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THE    TOXEMIAS 
OF   PREGNANCY 


« •• 


o57 


THE  TOXEMIAS 
OF    PREGNANCY 


BY 


GEORGE  WILLIAM  jKOSMAK,  A.B.,  M.D.,  F.A.C.S. 

ATTENDING  BURGEON,    LYING-IN  HOSPITAL;     EDITOR,    AMERICAN  JOURNAL 
OF   OBSTETRICS  AND   GYNECOLOGY 


D.  APPLETON  AND  COMPANY 

NEW  YORK  LONDON 

1922 


COPYRIGHT,   1922,   BY 

D.  APPLETON  AND  COMPANY 


PRINTED  IN  THE  UNITED  STATES  O»  AMERICA 


Btamilcal 
Library 


PREFACE 

The  toxemias  of  pregnancy  constitute  a  group  of  complica- 
tions of  the  period  of  gestation  which,  in  so  far  as  a  true  knowl- 
edge of  their  processes  is  concerned,  is  still  largely  in  the  realm 
of  theory  and  speculation.  Notwithstanding  this  fact  a  fairly 
rational  understanding  of  this  subject  now  obtains  and  this  mono- 
graph will  attempt  a  presentation  of  the  facts  and  such  particular 
deductions  as  may  be  of  value  in  the  diagnosis  and  treatment  of 
these  abnormalities  of  the  pregnant  state. 

The  views  held  regarding  the  toxemias  of  pregnancy  have 
undergone  decided  modifications  since  the  early  assumption  that 
they  were  due  merely  to  aberrations  in  the  function  of  the  kidney 
or  liver.  It  is  now  more  generally  acknowledged  that  we  are 
dealing  rather  with  metabolic  disturbances  and  that  the  clinical 
manifestations  with  which  we  are  familiar  are  merely  the  expres- 
sions of  focalized  damage  to  the  organism.  In  the  present  work  it 
is  proposed,  after  tracing  the  development  of  our  knowledge  of 
the  subject,  to  take  up  the  etiology,  symptomatology,  and  pathol- 
ogy, including  the  more  recent  studies  in  the  chemistry  of  the 
blood  and  urine.  The  section  on  the  urine  has  been  contributed 
by  Dr.  F.  E.  Sondern,  of  New  York,  and  that  on  the  blood  by  Dr. 
J.  A.  Killian,  of  New  York,  to  both  of  whom  I  desire  to  express 
herewith  my  sense  of  obligation.  The  final  section  is  devoted  to 
treatment  and  prophylaxis  with  particular  attention  to  the  results 
accomplished  by  adequate  prenatal  care. 

I  desire  to  acknowledge  an  indebtedness  to  those  medical  friends 
and  colleagues  who  have  courteously  favored  me  with  many  valuable 
illustrations  from  original  sources  or  from  their  published  papers  and 
books.  I  hope  that  I  have  not  neglected  to  give  due  credit  in  every 
instance  to  these  in  the  text. 

GEORGE  W.  KOSMAK 

SNEw  YORK 


CONTENTS 

CHAPTER  PAGE 

I.    HISTORICAL i 

Earliest  references  to  toxemias  of  pregnancy  in  the  writings  of 
Hippocrates  and  Galen,  i — Derivation  of  "eclampsia,"  I — Refer- 
ences in  Italian  medical  works  of  the  Middle  Ages,  2 — Introduction 
of  term  into  French  and  German  medical  literature  in  the  eighteenth 
century,  2 — Early  English  observers,  3 — Distinction  between  hyper- 
emesis  and  eclampsia  in  early  part  of  nineteenth  century,  5 — Clinical 
knowledge  of  eclampsia  in  existence  for  several  centuries,  II — 
Modes  of  treatment,  u. 

II.    ETIOLOGY  AND  SYMPTOMATOLOGY 13 

Introductory,  13 — Hyperemesis  gravidarum,  15 — Etiology,  15 — Toxic 
and  psychic  factors,  15 — High  ammonia  coefficient,  15 — Hepatic 
lesions,  18 — Glycogen  deficiency,  19 — Acute  yellow  atrophy  of  the 
liver,  20 — Etiology,  20 — Differential  diagnosis,  20 — Bacterial  theory, 
21  —  Nephritic  toxemia,  21  —  Symptoms,  22  —  Pre-eclamptic  tox- 
emia, 23  —  Eclampsia,  23  —  Definition,  23  —  Frequency,  24  —  In- 
cidence, 24  —  Influence  of  seasons,  25  —  Mortality,  26  —  Clinical 
course,  27  —  In  puerperium,  29  —  Without  convulsions,  29  — 
Peripheral  nerve  lesions,  29  —  Blood  pressure,  30  —  Significance, 
31  —  Urine  in  eclamptic  seizure,  32  —  Role  of  kidneys,  33  — 
Frequency  of  renal  infection,  33 — Infections  other  than  renal, 

34  —  Dental    foci    of   infection,   34  —  Early   autolysis    of   placenta, 

35  —  Internal  gland  function,  41  —  Opotherapy,  41  —  Exophthalmic 
goiter  in  pregnancy,  41 — Effect  of  thyroidectomy  on  pregnancy,  42 
— Thyroid  and  parathyroid  opotherapy,  44 — The  mammary  gland 
theory,  44 — Experimental  confirmation,  45 — Criticism  of  theory,  45 
— Abstraction    of   calcium    salts,   46 — Intermediary   products,   46— 
Anaphylactic  reaction,  47 — Parenteral  introduction  of  complex  pro- 
tein, 48 — Leucin,  48 — Dissenting  views  on  sensitization,  48 — Prog- 
nosis for   fetus,  49 — Errors  of  metabolism,  50 — Influence  of  war 
diet,  50 — Variations  in  diet,  51 — Epilepsy  and  eclampsia,  differentia- 
tion of,  52 — Differentiation  of  uremia  and  eclampsia,  52 — Differen- 
tiation of  chorea  and  eclampsia,  53 — Mortality  of  chorea  in  preg- 
nancy, 53 — Symptoms  of  chorea  in  pregnancy,  53 — Differentiation 
of  eclampsia  from  hysterical  and  cerebral  convulsions,  54 — Increased 
salivation,  55 — Presumable  toxemias,  55 — Skin  eruptions,  55 — Pur- 
pura,  56 — Herpes,  56 — Pruritus,    56 — Urticaria,  57 — Angioneurotic 
edema,  57 — Prognosis  in  toxemias  of  pregnancy,  57 — Recurrence, 
58— Hospital  statistics,  58. 

III.    PATHOLOGY .63 

Hyperemesis,  64 — Hepatic  lesions,  64 — Evidence  of  fetal  origin,  65 — 
Renal  lesions,  65 — Hemorrhages,  66 — Interpretation  of  findings,  66 
— Acute  yellow  atrophy  of  the  liver,  66 — Hepatic  and  renal  lesions, 
66 — Schwangerschaftsleber,  69 — Nephritic  and  pre-eclamptic  tox- 
emias, 69 — Pathology,  69 — Functional  renal  tests,  70 — Eclampsia,  70 
— Renal  lesions,  70 — Hepatic  lesions,  72 — Histology,  74 — Hemor- 


viii  CONTENTS 

CHAPTER  RAGE 

rhages,  78 — Cerebral  edema,  80 — Hemorrhage  of  heart  and  other 
organs,  81 — Traumatic  lesions,  81 — Ocular  lesions,  82 — Placental 
infarcts,  83 — Origin,  83 — Differential  diagnosis,  86 — Conclusion,  86. 

IV.    TREATMENT 90 

General,  90 — Treatment  of  hyperemesis,  91 — Physical  examination, 
91 — Correction  of  retroflexion,  91 — Stenosis  of  cervical  canal,  92 — 
Cauterization  of  cervical  erosions,  93 — General  hygiene,  93 — Diet 
schedule,  95 — Corpus  luteum  extract,  95 — Prognosis,  96 — Routine 
of  care,  97 — Relief  of  thirst,  99 — Induction  of  abortion,  99 — Vaginal 
hysterotomy  in  primiparae,  102 — Shock,  103 — Hospital  care,  104 — 
Supplementary  measures,  104 — Sera  and  gland  extraction,  104 — 
Negative  results,  105 — Fetal  serum,  105 — Placental  extracts,  105 — - 
Nasopharyngeal  complications,  107 — Sedative  drugs,  107 — Opium, 
107 — Ipecac,  108 — Cocain,  menthol,  etc.,  108 — Blood  transfusion,  108 
— Acute  yellow  atrophy  of  liver,  109 — Nephritis  and  eclampsia,  109 
— Treatment  of  eclampsia,  no — Prophylactic  measures,  in — Con- 
stipation, 113 — Care  of  organs  of  elimination,  114 — Blood  pressure, 
115  —  Visual  disturbances, -n6 —  Convulsions,  116  —  Examinations, 
vaginal  and  rectal,  118 — Enemas  and  stomach  washing,  118 — Induc- 
tion of  labor,  118 — Delivery,  119 — Rectal  infusions,  119 — Desirability 
of  labor,  120 — Care  of  patient  after  labor,  121 — Urine  examinations, 
121 — After  care,  122 — Treatment  of  complications,  122 — Other  plans 
of  treatment,  123 — Comparative  mortality  rates,  125 — Cesarean  sec- 
tion, when  justifiable,  128 — Venesection,  129 — Decapsulation  of  the 
kidney,  130 — Case  reports,  130 — Skull  trephining  and  lumbar  punc- 
ture, 131 — Magnesium  sulphate  in  lumbar  puncture,  132 — Normal 
pregnancy  serum,  132 — Rectal  infusions  of  magnesium  sulphate,  133 
— Blood  transfusion,  133 — Ductless  glandular  opotherapy  and  sero- 
therapy, 133 — Flushing  through  the  stomach,  134 — Carbohydrates, 
135 — Intravenous  injection  of  glucose,  138— Glycemia  curve  as 
index  to  liver  impairment,  140 — Technic  of  glycemia  curve  esti- 
mates, 142 — Summary,  148. 

V.  URINARY  CONDITIONS  ASSOCIATED  WITH  THE  TOXEMIAS  OF  PREGNANCY  153 
Ammonia  coefficient,  154 — Amino-acids,  155 — Acidosis,  155 — Starva- 
tion, 155 — Bile  pigment,  155 — Urine  analysis  with  special  reference 
to  the  diagnosis  of  toxemia  of  pregnancy,  156 — Volume,  156 — 
Solids,  156 — Urea,  156 — Chlorids,  156 — Indican,  157 — Albumin  and 
casts,  157 — Nitrogen  partition,  158 — Acidosis,  159 — Urobilin  and 
bile  pigment,  159 — Differential  diagnosis,  160 — Toxemias  of  preg- 
nancy, 160  —  Stasis  and  renal  hyperemia,  162  —  Nephritis,  162  — 
Chronic  interstitial,  163 — Chronic  parenchymatous,  163. 

VI.    SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD  IN  THE  TOXEMIAS  OF 

PREGNANCY 166 

Chemical  analysis,  166 — Nonprotein  nitrogen,  167 — Urea  nitrogen,  169 
— Rest  nitrogen,  169 — Distribution  of  nonprotein  nitrogen,  169 — 
Uric  acid,  170  —  Retention,  171  —  Increase,  171  —  Creatinin,  171  — 
Chlorids,  173 — Alkali  reserve,  175 — Carbon  dioxid,  how  determined, 
177 — Normal  pregnancy,  178 — Blood  changes,  178 — Nephritic  tox- 
emias, 179 — Blood  changes,  179 — Acute  yellow  atrophy  of  the  liver, 
182 — Blood  changes,  182 — Hyperemesis,  183 — Blood  changes,  183 
— Carbon  dioxid  combining  power,  decrease  of,  183 — Pre-eclampsias 
and  eclampsias,  186 — Blood  changes,  186 — High  protein  nitrogen, 


CONTENTS  ix 

CHAPTER  PAGU 

186 — Uric  acid  concentration,  187 — Hyperglycemia,  192 — Nonprotein 
nitrogen  distribution,  193 — Umbilical  vein  and  artery,  194 — Cerebro- 
spinal  fluid,  193 — Summary,  196  . 

ILLUSTRATIVE  CASE  REPORTS 

Severe  hyperemesis  in  first  pregnancy  with  complete  absence  of  this 
complication  in  subsequent  pregnancies,  199 — Induction  of  labor  for 
death  of  fetus  and  toxemia,  200 — Induction  of  labor  for  mild 
toxemia,  202 — Induction  of  labor  for  nephritic  type  of  toxemia,  203 
— Eclampsia  during  midpregnancy  in  a  patient  with  chronic  neph- 
ritis, 203 — Induction  of  labor  for  toxemia  and  thyroid  disturbances, 
204 — Induction  of  labor  for  hydramnios  with  mild  toxemia  and 
thyroid  disturbance,  205 — Doubtful  eclampsia  with  a  single  con- 
vulsion, 206 — Pre-eclamptic  toxemia  with  induction  of  labor,  cer- 
vical incision  and  forceps  delivery,  206 — Confusion  of  eclampsia 
with  encephalitis  lethargica,  207 — Cardiac  disease  associated  with 
toxemia  at  seventh  month,  208— Pre-eclamptic  toxemia,  with  cesa- 
rean  section,  208 — Fulminating  eclampsia  with  recovery  and  sub- 
sequent death  from  cerebral  hemorrhage,  209 — Induction  of  labor 
for  recurrent  albuminuria,  210 — Induction  of  labor  for  progressive 
toxemia,  210 — Toxemia  of  the  seventh  month  with  premature 
separation  of  placenta  at  term,  211 — Marked  toxemia  in  middle 
months  of  pregnancy,  212 — Spontaneous  abortion  during  toxemia, 
213 — Cesarean  section  for  eclampsia  in  first  pregnancy;  second 
pregnancy  and  labor  normal,  213 — Convulsions  due  to  cerebral 
abscess  during  pregnancy  which  closely  simulated  eclampsia,  214 — 
Fatal  case  of  hepatic  type  of  eclampsia,  214 — Induction  of  abortion 
for  toxemia  in  the  middle  months  of  pregnancy,  215 — Eclamptic 
patient  delivered  by  vaginal  cesarean  section,  216 — Induction  of 
labor  for  chronic  nephritis  with  visual  complications,  216 — Fatal 
case  of  eclampsia  of  the  nephritic  type,  217 — Eclampsia  with  induc- 
tion of  labor,  version  and  death  of  patient,  218— Diabetic  coma 
diagnosed  as  eclampsia,  219 — Numerous  eclamptic  convulsions  with 
recovery  after  sedative  treatment,  219, 


ILLUSTRATIONS 

FIGURE  PAGE 

1.  Graphic  chart  showing  urinary  conditions  in  a  case  of  neurotic  vomiting 

with    starvation 16 

2.  Graphic  chart  showing  ammonia  coefficient  in  two  successive  pregnancies  17 

3.  Urinary  chart  from  a  case  of  toxemic  vomiting 18 

J  4.     Graphic  chart  showing  the  incidence  of  eclampsia  in  different  seasons       .  25 

5.  Urinary  chart  from  a  case  of  eclampsia  with  recovery  showing  the  total 

nitrogen  ammonia  and  albumin 32 

6.  Section  of  the  placenta  from  a  case  of  albuminuria 37 

7.  Section  of  a  placenta  from  a  case  of  eclampsia 38 

8.  Section  of  placenta  from  a  case  of  severe  albuminuria  .       .       .       .       .  39 

9.  Section  of  placenta  from  a  case  of  acute  toxemia 40 

10.  Section  of  liver   from  a  fatal  case  of  vomiting  of  pregnancy  showing 

central  necrosis 64 

11.  Section  of  liver  from  a  case  of  acute  yellow  atrophy  showing  destruction 

of  all  but  a  few  groups  of  liver  cells 67 

12.  Section  of  liver,  under  high  power,  of  a  case  of  acute  yellow  atrophy, 

showing  fatty  degeneration  of  necrosis  of  liver  cells 68 

13.  Section  of    a  kidney  from  a  case  of  acute  yellow  atrophy  of  the  liver       .  69 

14.  Section  of  kidney  from  a  case  of  eclampsia 71 

15.  Section  of  kidney  from  a  case  of  eclampsia  showing  tubules  filled  with 

hyaline  and  granular  detritus 72 

16.  Liver   from  an   eclamptic 73 

17.  Liver  from  a  case  a  case  of  eclampsia,  showing  extended  distribution  of 

subcapsular  hemorrhages 74 

18.  Cross  section  of  liver  from  a  case  of  eclampsia,  showing  periportal  necrosis  75 

19.  Section  of  liver  from  a  case  of  eclampsia  under  high  power  ....  76 

20.  Section  of  a  liver  from  a  case  of  eclampsia 77 

21.  View  of  the  brain  laid  open,  from  a  case  of  postpartum  eclampsia  .       .  79 

22.  Brain  laid  open,  from  a  case  of  eclampsia  with  convulsions  ....  80 

23.  Blood  pressure  chart  from  a  case  of  eclampsia  in  which  rapid  delivery 

was  done  and  veratrum  viride  was  given 100 

xi 


xii  ILLUSTRATIONS 

FIGURE  PAGE 

24.  Blood  pressure  chart  from  a  pre-eclamptic  case,  showing  rapid  fall  after 

the  administration  of  veratrum  viride  alone 101 

25.  Blood   pressure   chart   from    a   case   of    eclampsia   with   twins,    showing 

temporary  reduction  after  delivery  but  with  final  recovery  .       .       .     102 

26.  Blood  pressure  chart   from   a  pre-eclamptic,   showing  little   effect   from 

veratrum   viride I2O 

27.  Section  of  kidney  of  dog  subjected  to  chloroform  anesthesia  .       .       .     137 

28.  Section  of  kidney  of  dog  after  seven  and  one-half  hours  of  chloroform 

anesthesia 138 

29.  Section  of  liver  of  dog  after  two  hours  of  chloroform  anesthesia      .       .     139 

30.  Section  of  liver  from  a  case  of  toxemia  after  intravenous  glucose  injection     140 

31.  Section  of  liver  from  a  case  of  eclampsia,  showing  swollen  cells,  poorly 

outlined,  coarsely  pigmented 141 

32.  Section  of  liver  from  a  case  of  eclampsia,  showing  extreme  cloudy  swell- 

ing of  cells 142 

33.  Section  of  liver  from  a  case  of  acute  yellow  atrophy  in  early  pregnancy, 

showing   swollen,   turbid  cells 143 


THE    TOXEMIAS 
OF   PREGNANCY 


TOXEMIAS  OF  PREGNANCY 


CHAPTER  I 
HISTORICAL 

Earliest  references  to  toxemias  of  pregnancy  in  the  writings  of  Hippocrates  and 
Galen — Derivation  of  "eclampsia" — Occasional  references  in  Italian  medical 
works  of  the  Middle  Ages — Introduction  of  term  into  French  and  German 
medical  literature  in  the  eighteenth  century  —  Mauriceau  —  Amberg  —  Early 
English  observers — Burton,  1751 — Hamilton,  1781 — Distinction  between  hyper- 
emesis  and  eclampsia  in  early  part  of  nineteenth  century,  Bard,  1815 — Clinical 
knowledge  of  eclampsia  in  existence  for  several  centuries — Modes  of  treatment 
by  purgation,  venesection,  sedatives  and  alkalies — Prophylaxis  a  much  later 
development — Gene'ral  interest  in  subject  shown  by  voluminous  literature. 

The  task  of  writing  a  historical  introduction  to  this  subject  is 
lightened  by  the  usual  procedure  adopted  by  most  medical  writers  of 
going  back  to  the  fathers  of  all  things  medical,  Hippocrates  and  Galen, 
for  the  necessary  beginnings.  In  their  treatises  as  they  have  come 
down  to  us,  we  find  numerous  though  rather  confused  references  to 
the  diseases  recognized  to-day  as  the  toxemias  of  pregnancy.  Such 
irregularities  in  the  normal  course  of  gestation  as  manifested  by 
constitutional  disturbances  were  usually  attributed  to  retention  of 
various  "humours,"  and  while  distinct  references  are  made  both  to 
excessive  vomiting  and  convulsive  seizures,  there  are  no  specific 
explanations  offered  as  to  their  cause,  nor  definite  recommendation  for 
their  treatment.  That  the  more  violent  manifestation  of  the  toxemias 
of  pregnancy  were  recognized  in  the  time  of  Hippocrates  may  be 
gathered  from  the  fact  that  the  derivation  of  our  word  "eclampsia" 
is  from  the  Greek  6K\afj.ir^,  which,  meaning  "flash"  and  conveying 
the  idea  of  a  sudden  onset,  was  used  by  this  writer  to  designate  a 
rapidly  developing  fever.  We  find  the  word  revived  by  Sauvage, 
who  employed  the  term  in  his  writings  and  in  a  work  published  in 
1796,  Gehler,  taking  it  from  the  latter,  introduced  it  into  German 
medical  literature.  It  was  not  until  the  beginning  of  the  last  century, 
however,  that  "eclampsia"  superseded  the  more  general  designation  of 


2  TOXEMIAS  OF   PREGNANCY 

"convulsions"  as  an  appellation  descriptive  of  the  principal  symptom 
associated  with  this  complication  of  pregnancy.  The  occurrence  of 
gestation  in  epileptic  women  led  to  confusion  which  persisted  for  a 
long  time  and  we  find  that  many  writers  in  the  early  part  of  the  nine- 
teenth century  still  regarded  the  convulsions  in  the  latter  months  of 
pregnancy  as  epileptic  seizures. 

Occasional  references  are  found  in  the  Italian  medical  works  of  the 
Middle  Ages,  but  it  is  not  until  the  eighteenth  century  that  we  meet 
with  well  recognized  descriptions  of  the  toxemias  of  pregnancy. 
Mauriceau,  writing  in  the  latter  part  of  the  seventeenth  century,  pre- 
sents certain  definite  notions  of  these  disorders.  He  attributes 
intractable  vomiting  to  the  cessation  of  menstruation,  which  caused 
"corrupt  humours  cleaving  to  the  insides  of  the  stomach,  which 
being  impossible  to  be  evacuated  by  so  many  preceding  vomitings 
because  they  adhere  so  fast,  must  be  purged  away  by  stool;  to  effect 
which  they  need  a  dissolvent,  which  may  be  a  gentle  purge  ...  In 
perturbations  and  dejections  of  the  belly,  and  in  spontaneous  vomit- 
ings, if  the  matter  be  purged  away,  the  patient  finds  ease  and  comfort; 
if  not,  the  contrary  ...  If  the  vomiting  continues  daily,  almost 
without  intermission,  although  the  woman  observes  a  good  diet,  and 
after  she  hath  been  reasonably  purged,  we  must  rest  there,  lest  some- 
thing worse  happen,  for  which  we  may  incur  the  blame;  she  being 
then  in  great  danger  of  miscarriage.  And  when  the  hiccough  takes 
them  through  emptiness  proceeding  from  too  much  evacuation  caused 
by  these  continual  vomitings,  it  is  very  bad." 

Amberg  reported,  in  1713,  his  observations  on  convulsions,  which 
are  interesting  enough  to  be  repeated  in  detail.  He  describes  the  case 
of  a  young  lady  twenty-six  years  of  age  "who  had  gone  about  one-half 
her  time  with  child  and  had  not  yet  been  bled,  was  invaded  with  con- 
vulsions of  the  hands,  feet,  head,  mouth,  and  cheeks,  which  terrified 
her  greatly,  and  rendered  her  apprehensive  of  their  being  succeeded 
by  an  apoplexy  or  epilepsy."  She  consulted  Dr.  Amberg  who  pre- 
scribed as  follows:  "Phlebotomy  in  the  arm  immediately  to  eight 
ounces.  A  teaspoonful  every  morning  of  a  'nervous  powder'  to  be 
repeated  in  the  afternoon  at  four  o'clock  and  at  bedtime."  The 
majority  of  the  ingredients  of  this  powder  cannot  be  duplicated  in 
the  present-day  pharmacopoeia,  but  were  evidently  designed  for  their 
refrigerant  and  laxative  effects.  Amberg  states  that,  after  continuing 
these  medicines  for  two  days,  she  "perceived  no  more  of  her  con- 
vulsions, and  she  was  happily  delivered  of  a  healthful  child." 


HISTORICAL  3 

Burton,  in  his  essay  Tozvards  a  New  System  of  Midwifery, 
London,  1751,  in  the  part  devoted  to  the  diseases  of  pregnant  women, 
repeats  the  earlier  contention  that  some  of  these  disorders  arise  solely 
from  the  stoppage  of  the  menstrual  flux;  others  from  the  motions  and 
bulk  of  the  fetus,  secundines  and  waters.  He  claims  that  the  "stoppage 
of  the  menstrual  flux  causes  vomiting,  loss  of  appetite,  nausea,  faint- 
ings,  vertigo,  pains  in  the  stomach,  shortness  of  breath  and  cough,  all 
of  which  generally  abate  about  the  third  month  of  pregnancy,  or 
sooner.  From  the  second  cause  also  proceed  vomiting,  shortness  of 
breath,  cough,  incontinence  and  suppression  of  urine,  and  constipation. 
Likewise  pains  in  the  back  and  groin,  varices,  piles,  and  swellings  of 
the  legs,  thighs  and  pudenda."  "These  vomitings,"  he  states,  "seem 
to  be  occasioned  by  various  causes  which  require  different  methods  of 
relieving  them.  First,  they  may  be  caused  by  too  great  a  distention  of 
the  blood  vessels,  whereby  the  nerves  may  be  so  pressed  as  to  occasion 
that  convulsive  motion  of  the  diaphragm,  stomach,  bowels  and  abdom- 
inal muscles  which  we  call  vomiting.  Secondly,  the  vomiting  may  be 
occasioned  by  the  remains  of  undigested  food,  being  either  too  great 
in  quantity  or  by  being  too  acrimonious."  The  second  cause,  he  more- 
over observes,  "may  proceed  from  too  great  extension  of  the  womb, 
which  sometimes  will  rise  over-high  in  the  abdomen,  especially  in 
people  whose  bones  that  form  the  lower  part  of  the  hypogastric  region, 
are  too  straight,  or  as  it  is  commonly  called  'straight-hipped'  .  .  . 
The  appetite  very  often,  nay  generally,  is  depraved  from  the  beginning 
of  pregnancy,  for  the  blood  vessels  being  so  much  distended,  by  press- 
ing on  the  nerves  may  hinder  their  action,  so  as  to  prevent  their  use  in 
causing  the  sensation  of  hunger.  Sometimes  also  this  may  proceed 
from  the  little  consumption  of  the  humours,  the  vessels  being  full; 
whence  nature  has  not  as  great  a  demand,  as  the  child  consumes  so 
little ;  and  as  the  mother  seems  to  perspire  less  than  usual,  as  appeared 
from  the  seeming  heaviness  and  torpor,  which  pregnant  women  so 
often  complain  of." 

An  interesting  reference  to  "convulsions  and  lethargy  occurring 
in  labor"  is  found  in  a  treatise  by  Madame  Le  Boursier  du  Coudray, 
Chief  Midwife  of  Paris,  published  in  1777. 

"It  sometimes  happens  that  a  woman  will  have  convulsions  before 
she  goes  into  labour.  If  such  an  accident  happens,  a  competent  doctor 
or  surgeon  should  be  called,  as  the  condition  is  dangerous  to  both 
mother  and  child,  and  a  careful  examination  should  be  made  to  find 


4  TOXEMIAS  OF  PREGNANCY 

out  just  how  they  are  doing.  While  awaiting  this  assistance,  the 
patient  should  be  bathed  with  pure  water,  and  care  should  be  taken 
that  none  of  it  be  allowed  to  touch  her  face  or  her  throat,  as  this  will 
increase  the  violence  of  the  convulsions,  as  will  likewise  spirituous 
liqueurs.  If  labor  begins  during  the  convulsion,  and  the  child  presents 
well,  there  is  hope  for  the  patient  and  delivery  should  be  hastened  as 
much  as  possible.  If  there  be  a  bad  presentation,  or  version  must  be 
done,  this  will  serve  to  greatly  increase  the  irritation  of  the  nervous 
system  already  so  greatly  disturbed;  therefore  it  is  better  to  await 
patiently  the  course  of  nature  .  .  .  There  is  another  state  apt  to  prove 
fatal  to  the  woman,  that  is  when  she  falls  into  a  lethargy;  all  the 
resources  of  the  animal  economy  being  exhausted,  so  that  there  is 
nothing  left  to  assist  her  in  giving  birth  to  the  child.  Under  these  con- 
ditions it  is  necessary  to  make  delivery  as  promptly  as  possible,  as  that 
is  the  sole  hope  of  saving  the  mother's  life.  I  have  often  found  myself 
in  both  the  situations  above  outlined,  and  having  called  in  skilled  and 
competent  (medical)  people,  I  am  able  to  state  that  none  of  my 
mothers  died,  and  I  was  able  even  to  deliver  some  living  children." 

Hamilton,  in  his  Treatise  on  MidTtrifery,  published  in  Edinburgh 
in  1781,  refers  to  the  alteration  in  the  blood  in  the  pregnant  state 
which  may  account  for  many  of  the  symptoms  of  pregnancy;  par- 
ticularly the  appearance  of  a  general,  and  sometimes  of  a  local, 
plethora.  He  believes,  however,  that  "many  of  the  symptoms  appear 
to  be  entirely  of  the  nervous  kind,  and  not  readily  explicable  ...  In 
the  advanced  states  of  pregnancy  the  pressure  of  the  uterus  on  the 
surrounding  parts  produces  many  complaints."  He  refers  to  con- 
vulsions during  pregnancy  as  possibly  occurring  in  the  early  months, 
although  more  common  in  the  latter  months,  and  at  the  commence- 
ment of  labor.  He  states  that  the  "appearance  of  epileptic  fits  in 
pregnant  women  is  frightful;  the  symptoms  are  alarming;  and  the 
event  is  always  precarious,  often  fatal."  It  is  interesting  to  note 
Hamilton's  description  of  the  prodromal  stage  of  which  he  says  "head- 
ache, intolerably  violent,  or  tense  pain  or  oppression  about  the  prae- 
cordia,  are  the  most  common  presaging  symptoms."  The  exciting 
cause  he  believes  to  be  "uterine  irritability  communicated  by  sympathy 
to  the  encephalon,  in  some  instances  probably  originating  from  the 
struggle  or  convulsive  motions  of  the  fetus,  arising  from  its  awkward 
or  hampered  position,  and  pressure  of  the  gravid  uterus  interrupting 
the  circulation  through  the  abdominal  viscera,  disturbing  their  func- 


HISTORICAL  5 

tions  and  changing  the  determination  both  of  the  circulating  fluid  and 
nervous  energy."  Hamilton,  it  is  stated  in  a  footnote  by  Dr.  Burns, 
was  among  the  first  English  writers  to  employ  the  term  "eclampsia." 

In  an  English  book  by  S.  H.  Jackson  published  in  London,  1801, 
entitled  Cautions  to  Women  Respecting  the  State  of  Pregnancy,  the 
writer,  in  describing  the  irritations  of  the  stomach,  claims  that  it  would 
be  nearer  the  truth  "if  we  suppose  them  to  arise  either  from  pressure 
against  the  inside  of  the  liver  and  gall-bladder,  or  on  the  great  vessels 
belonging  to  the  heart.  This  pressure  is  most  likely  to  occur  in  persons 
of  small  stature  and  it  is  not  infrequently  accompanied  by  some 
degree  of  jaundice." 

In  the  early  years  of  the  nineteenth  century  we  begin  to  find  more 
clear-cut  references  to  hyperemesis  and  eclampsia.  In  Heath's 
Translation  of  Baudelocque's  Midwifery,  published  in  Philadelphia  in 
1807,  puerperal  convulsions  are  stated  "to  depend  on  sudden  and 
great  emotions  of  the  mind,  or  a  sanguine  plethora,  or  an  excessive 
flooding,  or  on  a  fullness  of  the  primae  viae,  on  an  extreme  sensibility 
of  the  uterine  fibers,  a  violent  distention  of  the  edge  of  the  orifice  of 
the  uterus,  and  of  the  parts  which  form  the  entrance  of  the  pudendum. 
.  .  .  The  occurrence  of  all  these  causes  is  not  necessary  to  produce 
convulsions;  a  single  one  is  sufficient.  All  convulsions  are  not  of  the 
same  nature  nor  affect  the  organs,  nor  equally  disturb  the  harmony 
of  the  functions.  Sometimes  they  present  a  frightful  spectacle,  at 
other  times  the  countenance  is  tranquil.  Sometimes  the  understanding 
does  not  return  for  hours  or  even  days  after  these  convulsions." 

In  Bard's  Compendium  of  Midwifery,  published  in  New  York  in 
1815,  we  find  extended  references  to  hyperemesis  and  convulsive 
seizures.  The  writer  insists  that  in  intractable  cases  of  vomiting  relief 
is  obtained  only  from  a  removal  of  five  to  six  ounces  of  blood  for 
three  or  four  successive  days  rather  than  at  one  time.  In  accordance 
with  the  belief  prevailing  at  that  date  he  describes  the  convulsions  of 
the  latter  months  of  pregnancy  as  "epileptic  fits"  to  which  women  are 
peculiarly  subject  in  pregnancy.  He  also  states  that  "women  who  are 
inhabitants  of  populous  cities  and  in  the  higher  spheres  of  life,  who 
have  been  delicately  bred  and  who  indulge  themselves  in  a  dissipated 
and  luxurious  life,  are  much  more  liable  to  these  dreadful  and  fatal 
diseases  than  the  more  hardy  inhabitants  of  the  country,  or  than  such 
as  from  constant  labor  and  exercise  enjoy  robust  constitutions." 
This  scarcely  agrees  with  our  observation  of  the  present  day  that 
eclampsia  is  as  prevalent  among  the  poor  as  among  the  well-to-do.  It 


is  probably  even  more  prevalent  ajnong  the  poor,  unless  proper  super- 
vision is  maintained. 

Bard  believes,  moreover,  that  "women  are  most  liable  to  convul- 
sions at  the  commencement  of  labor  when  the  first  dilatation  of  the 
extremely  sensitive  os  uteri  seems  to  bring  them  on.  They  are  more 
apt  to  occur  in  a  first,  than  in  subsequent  labors,  from  the  great 
apprehension  and  terror  which  some  women  suffer  on  that  occasion ; 
and  perhaps  for  a  similar  reason,  whose  labor  is  brought  on  by  some 
dangerous  accident,  some  sudden  stroke  of  affliction,  who  have  suf- 
fered convulsions  on  a  former  occasion,  and  those  unhappy  women, 
who,  instead  of  rejoicing  in  the  birth  of  the  child,  dread  consequent 
reproach  more  than  the  pain  and  danger." 

Further  interesting  observations  are  contained  in  the  paragraph  in 
which  Bard  states  that  "the  danger  of  convulsions  is  in  general  in  pro- 
portion to  the  advanced  state  of  pregnancy,  except  when  they  occur 
after  labor  pains  have  begun,  when  a  speedy  delivery  frequently 
carries  them  off;  in  other  respects  the  danger  is  to  be  estimated  more 
from  the  health  and  constitution  of  the  patient,  from  the  violence  of 
the  fits  and  from  the  stupor  and  apoplectic  symptoms  by  which  they 
are  succeeded,  than  from  the  frequency  of  their  recurrence.  When  each 
succeeding  fit  is  more  violent,  and  when  they  leave  the  patient  more 
and  more  comatose,  the  danger  is  most  imminent." 

The  conceptions  held  at  the  beginning  of  the  last  century  on  the 
toxemias  of  pregnancies  are  clouded  by  the  interpretation  which  these 
writers  placed  on  clinical  symptoms.  Thus,  John  Burns,  a  lecturer  on 
midwifery  in  the  medical  school  at  Glasgow,  designates  by  the  term 
"febrile  state,"  a  train  of  symptoms  now  recognized  as  purely  toxic  in 
character.  He  believes  that  in  such  cases  it  is  merely  necessary  to  keep 
the  bowels  open  and  to  take  away  a  little  blood.  Burns  also  describes 
another  so-called  "species  of  fever"  which  affects  women  about  the 
middle  of  pregnancy  and  makes  its  attacks  suddenly  like  a  "regular 
paroxysm  of  ague."  The  patient  complains  of  headache,  loathing  for 
food,  foul,  dry  tongue,  considerable  thirst,  and  is  constipated.  He 
states  that  the  disease  is  very  obstinate  and  often  ends  in  abortion, 
after  which,  if  the  women  do  not  sink  speedily,  they  begin  to  recover 
but  remain  long  in  a  "chlorotic  state  which,  if  not  relieved,  may 
terminate  in  phthisis."  He  even  suspects  that  this  disease  originates 
from  the  bowels  and  bears  a  "great  analogy  to  infantile  remitting 
fever." 

Burns,  in  another  chapter,  refers  to  headache  as  an'alarming  symp- 


HISTORICAL  7 

torn  and  in  connection  with  the  same  describes  very  satisfactorily  the 
syndrome  now  known  as  the  pre-eclamptic  stage,  characterized  by 
giddiness,  visual  disturbances,  etc.  In  such  circumstances,  he  says, 
"she  is  seized  with  apoplexy  or  epilepsy,"  and  believes  that  these  dis- 
eases are  to  be  prevented  by  immediate  recourse  to  bloodletting  and 
laxatives.  The  quantity  of  blood  which  is  to  be  removed  must  be 
determined  by  the  severity  of  the  symptoms,  the  habit  of  the  patient, 
and  the  effect  of  the  evacuations.  If  the  headache  is  accompanied  with 
edema,  digitalis  is  recommended  as  a  useful  addition  to  the  treatment. 
Burns  also  states  that  "if  the  patient  is  seized  with  apoplexy  there  is 
seldom  any  attempt  made  to  expel  the  child;  whereas  in  epilepsy  if 
the  paroxysm  be  protracted,  the  child  may  be  expelled  if  the  patient  be 
not  early  cut  off  by  a  fatal  coma.  In  some  instances  palsy  either  suc- 
ceeds an  apoplectic  attack  or  follows  headache  and  vertigo.  This  dis- 
ease does  not  commonly  go  off  until  delivery  takes  place,  but  it  may 
be  prevented  from  becoming  severe  by  mild  laxatives  and  light  diet." 

In  describing  edema  associated  with  pregnancy  Burns  mentions  the 
severe  cases  in  which  "epilepsy"  may  result.  When  the  edema  is 
severe  it  may  be  attended  with  convulsions  or  it  may  predispose  to 
puerperal  disease,  and  he  therefore  insists  that  the  edema  must  be 
reduced  by  bloodletting  and  purgatives. 

The  subject  of  vomiting  in  pregnancy  is  described  by  Burns  in  a 
very  interesting  manner,  especially  his  reference  to  the  necessity  in 
severe  cases  of  having  the  patient  refrain  from»eating  and  giving  her 
nourishing  "clysters."  Moreover,  if  the  vomiting  is  bilious  and  accom- 
panied with  pains  in  the  right  side  and  shoulder,  cough,  and  other 
symptoms  of  hepatitis,  a  seton  should  be  immediately  introduced  into 
the  side  and  a  very  gentle  course  of  mercury  given.  If  the  vomiting 
becomes  troublesome  at  the  end  of  pregnancy  "it  is  proper  to  detract 
blood  and  confine  the  patient  to  bed.  Cloths  dipped  in  laudanum 
should  be  applied  to  the  pit  of  the  stomach  and  a  grain  of  solid  opium 
given  internally."  But  he  does  not  say  anything  about  induction  of 
abortion  in  such  cases  nor  mention  the  possible  fatal  result. 

The  subject  of  eclampsia  is  also  dealt  with  by  Burns  in  the  chapter 
on  complicated  labor,  in  which  he  states  that  convulsions  of  various 
kinds  may  occur  either  during  pregnancy  or  labor.  One  species  is  the 
consequence  of  great  exertion,  excessive  fatigue,  tedious  labor,  or  pro- 
fuse hemorrhage.  The  attack  comes  on  without  much  warning  and 
generally  terminates  with  delirium.  The  muscles  about  the  face  and 
chest  are  chiefly  affected  and  the  pulse  is  small,  compressible,  and  fre- 


8  TOXEMIAS  OF  PREGNANCY 

quent,  the  face  pale,  the  eyes  sunk,  the  extremities  cold.  The  fits  suc- 
ceed very  quickly  and  soon  terminate  in  a  fatal  syncope.  In  treating 
the  condition  he  refers  to  the  necessity  of  keeping  the  patient  quiet,  and 
says  that  opium  is  of  great  service  and  that  delivery  is  usually  neces- 
sary. He  also  describes  hysterical  convulsions  as  more  common  dur- 
ing gestation  than  during  labor.  In  these  cases  there  is  no  foaming 
at  the  mouth,  no  working  with  the  tongue,  etc.  The  most  frequent 
species  of  puerperal  convulsions,  however,  is  epileptic,  which  occurs 
fifty  times  for  once  that  the  other  appears.  Convulsions  may  affect 
the  patient  suddenly  and  severely,  at  stool  or  sitting  in  a  chair.  Pres- 
ently, he  says,  the  convulsion  ends  in  a  short  stupor  from  which  the 
woman  awrakes  unconscious  of  having  been  ill,  but  in  a  short  time  the 
same  scene  is  generally  repeated ;  or,  perhaps,  although  the  convulsions 
have  gone  off,  the  stupor  remains.  It  is  not,  however,  unusual  for 
the  fit  to  be  preceded  by  some  Symptoms  which,  to  the  attentive 
observer,  indicate  its  approach.  These  are  headache,  pain  in  the  stom- 
ach with  unsupportable  sickness,  ringing  in  the  ears,  dazzling  of  the 
eyes  or  appearance  of  substances  floating  before  them,  slow  pulse,  and 
drowsiness  during  the  pains. 

How  well  the  above  description  fits  our  modern  conception  of  an 
eclamptic  seizure,  although  we  do  not  recognize  the  distinction  between 
"hysterical  epilepsy  and  the  other  convulsions."  It  is  very  likely  that 
most  of  the  cases  of  epilepsy  or  hysterical  convulsions  observed  by 
the  author  were  true  eclamptic  seizures.  He  admits  that  they  are 
dependent  on  the  pregnancy  but  goes  no  farther  in  advancing  any 
theory  as  to  their  causation.  Burns'  directions  for  treatment  are 
interesting.  In  the  first  place  he  cautions  against  injuries  to  the  tongue 
and  advises  the  insertion  of  a  piece  of  wood  between  the  teeth.  Next 
the  patient  should  be  bled,  or,  when  this  cannot  be  done,  further 
cupping  in  the  temples  and  back  part  of  the  neck  must  be  tried.  If  the 
convulsions  recur  the  bleeding  may  be  repeated,  and  he  believes  there 
is  more  danger  from  taking  too  little  blood  than  from  copious  evacua- 
tions. From  forty  to  eighty  ounces  of  blood  were  taken  from  some  of 
these  cases  of  puerperal  convulsions.  He  insists  that  bloodletting 
tends  to  relax  the  os  uteri.  After  this  a  "smart  clyster  is  given. 
The  head  is  then  shaved  and  blistered,  the  blister  being  proper  though 
the  fit  have  gone  off."  A  small  dose  of  calomel  or  solution  of  salts  may 
also  be  given  with  advantage  when  the  patient  can  swallow.  The 
bladder  must  likewise  be  emptied,  for  its  distention  may  cause  convul- 
sions. An  interesting  observation  is  that  the  depletion  reduces  the  risk 


HISTORICAL  9 

of  "fatal  oppression  of  the  brain  or  extravasation  of  blood  within  the 
skull  and  that  consequently  the  convulsion  is  mitigated."  Termination 
of  the  labor  is  advocated,  which  is  favored  by  the  bloodletting.  The 
dilatation  of  the  cervix  by  the  hand  should  be  resorted  to  and  the 
child  delivered  with  as  little  violence  as  possible.  Burns  believes  that 
the  use  of  medicaments,  such  as  opium,  musk  and  camphor,  is  not 
advisable  without  resort  to  the  other  procedures.  If  the  patient  is 
seen  before  the  fits  have  occurred,  preventive  treatment  includes 
emptying  the  bowels,  use  of  an  emetic  and,  in  the  presence  of  violent 
pains  in  the  stomach,  doing  a  venesection  and  giving  an  opiate.  The 
appearance  of  headache  also  calls  for  the  use  of  the  lancet.  Purga- 
tives, he  concludes,  are  a  very  important  part  of  the  treatment,  and 
he  has  had  better  results  from  this  than  other  methods,  which  makes 
him  incline  to  the  belief  that  an  "incorrect  state  of  the  bowels  is  one 
of  the  most  powerful  predisposing  causes  of  puerperal  convulsions, 
and  may  also  be  the  chief  exciting  cause." 

James  Blundell,  in  his  Principles  and  Practice  of  Obstetrics  (Am. 
ed.  1834),  devotes  considerable  space  to  the  subject  of  convulsions, 
and  the  following  extracts  from  his  book  are  of  interest.  Thus  he 
says: 

"Where  convulsions  do  not  actually  occur  there  is  sometimes  a  very 
obvious  tendency  to  the  attack,  flushing  of  the  face,  throbbing  of  the 
carotids,  severe  pains  in  the  head,  and  sensations  of  the  brain,  as  if  it 
were  too  large  for  its  receptacle,  which,  indeed,  in  a  certain  sense,  it  is, 
in  consequence  of  the  blood  flowing  into  it  too  copiously." 

"Unhappily  for  the  safety  of  the  patient,  she  may  be  seized  without 
premonitory  symptoms;  still,  however,  premonitory  signs  sometimes 
occur.  Tremors  of  the  whole  muscular  system,  shudderings,  crampy 
pains  in  the  region  of  the  stomach,  cerebral  afflux  of  blood,  flushing 
and  tumidity  of  the  face,  throbbing  of  the  carotid  arteries,  severe  and 
splitting  pains  of  the  head,  stammering,  and  perhaps  failure  of  utter- 
ance, constitute  some  of  the  leading  prognostics.  Sometimes  the 
patient  becomes  deaf,  and  more  frequently  her  sight  is  affected, 
dazzled  with  light,  or  blinded.  When  the  fit  supervenes,  the  woman 
becomes  entirely  insensible,  and,  together  with  this  insensibility,  she 
has  a  violent  commotion  of  the  voluntary  muscles.  .  .  .  When  these 
attacks  have  continued  ...  a  few  minutes  ...  we  find  the  patient 
recovering  [but]  sometimes  the  patient  lies  deaf  or  blind  or  incapable 


I0  TOXEMIAS  OF  PREGNANCY 

of  speaking  ...  as  if  the  sensorium  had  received  some  permanent 
injury. 

"Causes  of  convulsions:  The  immediate  causes  are  very  obscure; 
they  appear  sometimes  to  depend  upon  a  loaded  state  of  the  vessels  of 
the  brain ;  at  other  times  the  brain  appears  to  be  influenced  by  distant 
irritations,  either  in  the  uterus,  or  in  the  digestive  organs,  and  again, 
in  some  cases,  puerperal  convulsions,  are  induced,  apparently  by  a 
peculiar  irritability  of  the  nervous  system. 

"That  the  uterine  organs  are  in  some  way  implicated  is  evident, 
from  the  convulsions  being  of  a  character  .  .  .  peculiar  to  the  state 
of  either  pregnancy  or  parturition.  Some  writers  assign  three  especial 
causes  which  may  give  rise  to  this  disease,  namely,  general  irritability 
of  the  constitution,  irritability  of  the  uterus  from  distension  and  an 
overloaded  state  of  the  system. 

"The  custom  of  manner  of  living,  the  seasons  or  climate,  and  the 
general  state  of  the  health  of  the  patients,  are  not  wholly  undeserving 
of  being  classed  among  the  causes  of  these  convulsions. 

"To  persons  prone  to  cerebral  afflux,  convulsions  may  occur  in  the 
middle  and  earlier  months  sometimes,  but  still  more  frequently  in  the 
end  of  pregnancy. 

"When  convulsions  attack  a  patient  in  the  progress  of  gestation, 
she  may  have  a  single  fit  only  or  several,  the  intervals  being  usually 
irregular  and  somewhat  long,  not  of  a  few  minutes  only,  but  of  hours 
perhaps,  or  even  days. 

"Sooner  or  later,  if  the  fit  continues,  parturition  of  itself  com- 
mences. This  can  happen  ...  in  those  cases  also  in  which  the  dis- 
ease is  associated  with  apoplexy,  so  that  during  the  whole  time  the 
woman  is  either  comatose  or  convulsed.  ...  Be  at  the  bedside,  there- 
fore, in  these  convulsive  cases,  and  watch,  for  as  the  paroxysms  return 
the  labor  may  advance,  and  the  fetus  may  suddenly  emerge. 

"Should  you  ask  me,  in  what  manner  convulsions  are  produced,  I 
should  reply  that  the  more  probable  and  immediate  cause  of  them  is 
a  pressure  on  the  brain,  and  perhaps  on  the  spinal  marrow  also.  This 
pressure  sometimes  results  from  the  effusion  of  blood,  still  more  fre- 
quently from  the  effused  water,  and  most  frequently  of  all  from  mere 
congestion.  .  .  .  An  increased  action  of  the  vessels  produces  an 
accumulation  of  blood  in  the  genitals,  in  the  wattles  of  birds,  and  in 
the  breasts  of  women  during  suckling  and  ...  I  think  it  is  not 
improbable  that  in  these  convulsions  and  convulsive  propensities  of 
women,  a  cerebral  congestion,  with  pressure  and  irregular  circulation, 


HISTORICAL  Ii 

and  an  increased  action  of  the  carotid  and  vertebral  arteries,  have  a 
large  share  in  producing  the  disease. 

"In  the  end  of  gestation  women  are  sometimes  attacked  with 
apoplexy,  in  which  condition  they  may  be  for  hours  or  days,  recover- 
ing gradually  afterward  or  ultimately  sinking.  Under  apoplectic 
attacks,  I  believe,  labor  does  not  so  readily  come  on  as  under  con- 
vulsive attack;  nevertheless,  I  would  advise  you  to  examine  the  os 
uteri  occasionally,  and  take  care  that  the  child  is  not  born  unperceived. 
In  its  nature,  though  there  are  no  spasms,  I  look  upon  this  disease  as 
strictly  analogous  to  the  convulsions  of  which  I  have  been  speaking, 
and  I  would  therefore,  treat  it  upon  the  same  principle." 

I  have  quoted  a  certain  number  of  historical  references  in  extenso 
to  show  that  the  clinical  knowledge  of  the  toxemias  of  pregnancy  has 
been  in  existence  for  several  centuries  and  that  methods  of  treatment 
now  in  use  were  then  employed  for  similar  purposes,  including  purg- 
ing, venesection,  and  the  administration  of  sedatives  and  alkalies.  It 
is  perhaps  rather  discouraging  to  be  compelled  to  make  an  admission, 
in  reviewing  the  history  of  this  subject,  that  we  have  not  made  any 
noteworthy  advances  except  in  a  better  knowledge  of  associated 
pathology  and  the  chemistry  of  the  urine  and,  more  recently,  the 
chemistry  of  the  blood.  The  clinical  picture  of  an  eclamptic  seizure 
painted  by  Burns  in  1811  is  not,  except  for  certain  details,  very  far 
removed  from  that  described  in  modern  obstetrical  textbooks.  Nor 
have  we  determined  with  any  degree  even  approximating  to  certainty, 
what  are  the  precise  etiological  factors  underlying  the  production  of 
these  various  abnormalities  in  the  pregnant  state.  This  uncertainty 
regarding  etiology  makes  our  modern  modes  of  treating  hyperemesis, 
eclampsia  and  the  other  toxemias,  largely  empirical.  For  example, 
whether  to  resort  in  the  treatment  of  eclampsia  to  immediate  delivery, 
or  to  employ  palliative  measures  is  a  question  by  no  means  settled,  and 
arrays  of  facts  and  figures  are  presented  by  both  groups  of  observers, 
radical  and  conservative,  in  defense  of  their  individual  claims.  The 
incidence  and  the  mortality  of  the  toxemias  of  pregnancy  still  remains 
high,  although  recent  years  have  v/itnessed  great  improvement,  par- 
ticularly in  eclampsia,  where  preventive  measures  have  undoubtedly 
proved  their  value.  But  there  is  much  yet  to  be  learned,  and  before  us 
is  a  task  worthy  of  the  earnest  attention  of  medical  investigators,  in 
which  the  combined  thought  and  labor  of  clinician  and  laboratory 
worker,  rather  than  either  alone,  must  be  brought  to  bear  on  the  prob- 


12  TOXEMIAS  OF  PREGNANCY 

lem.  It  is  problematical  where  the  search  will  lead  us  and  what  epoch- 
making  discovery  will  reveal  one  or  more  etiological  factors  that  will 
serve  as  a  basis  for  rational  therapeutics.  Or,  perhaps,  prophylaxis 
alone,  as  in  so  many  other  diseases,  will  point  the  way  to  an  eradica- 
tion of  these  serious  complications  of  the  pregnant  state. 

A  condition  so  widespread  and  often  so  disastrous  in  its  effects  as 
the  toxic  disorders  of  pregnancy  has  been  a  stimulus  to  many  workers, 
and  medical  literature  is  so  crowded  with  references  that  it  would  be 
impossible  to  present  them  even  in  resume  within  the  limits  of  this 
volume.  It  has,  therefore,  seemed  advisable  to  include  under  each 
subdivision  a  general  descriptive  account  of  the  subject,  followed  by 
brief  references  to  the  more  important  original  works,  which  are  thus 
available  for  further  reading  and  consultation. 

LITERATURE 

BARD,  SAMUEL.    Compendium  on  Midwifery.    New  York,  1815. 
BLUNDELL,  JAMES.     Principles  and  Practice  of  Obstetrics  (Am.  ed.). 

1834- 

BURTON,  JOHN.  Essay  towards  a  New  System  of  Midwifery.  Lon- 
don, 1751. 

BURNS,  JOHN.  The  Principles  of  Midwifery  (3d  Am.  ed.,  from  2d 
London  ed.,  by  Thomas  C.  James).  Philadelphia,  1813. 

CONDRAY,  MME.  LE  BOURSIER  DU.  Abrege  de  1'art  des  accouchements. 
Paris,  1777. 

DEMEES,  W.  P.  A  Treatise  on  the  Diseases  of  Females  (8th  ed.). 
Philadelphia,  1843. 

GEHLER,  J.  G.  Kleine  Schriften  iiber  Entbindungskunst.  Leipzig, 
1796. 

HAMILTON,  ALEX.    Treatise  on  Midwifery.    Edinburgh,  1871. 

HEATH.  Translation  of  Baudelocque's  Midwifery.  Philadelphia, 
1807. 

HIPPOCRATES  AND  GALEN.  The  Writings  of  (ed.  by  J.  R.  Coxe). 
Philadelphia,  1846,-  Lindsay  and  Blakiston. 

JACKSON,  S.  H.  Cautions  to  Women  Respecting  the  State  of  Preg- 
nancy (2d  ed.).  London,  1801. 

MAURICEAU,  F.  Traite  des  maladies  des  femmes  grosses  (ed.  iv). 
Paris,  1694. 


CHAPTER  II 

ETIOLOGY  AND  SYMPTOMATOLOGY 

Autointoxication  long  considered  the  principal  etiological  factor — Disturbances  in 
metabolism  claimed  to  be  basis  of  varying  clinical  manifestations  of  a  single 
condition — This  theory  combated  especially  by  Williams — Histologic,  blood  and 
urine  studies  indicate  essential  differences — No  specific  principles  thus  far 
isolated  nor  specific  pathologic  lesions  recognized — Classification  of  pregnancy 
toxemias — Hyperemesis  gravidarum,  toxic  and  psychic  factors — Hepatic  lesions 
• — Glycogen  deficiency — Acute  yellow  atrophy  of  the  liver — Differential  diag- 
nosis— Bacterial  theory — Nephritic  toxemia — "Kidney  of  pregnancy" — Symp- 
toms— Specific  toxic  factor  as  etiology — Pre-eclamptic  toxemia — Difficult  to 
draw  distinction  between  this  and  former  symptoms — Eclampsia — Definition — 
Frequency  —  Incidence  —  Influence  of  seasons  —  Mortality  —  Clinical  course  — 
Ante-,  intra-  and  post-partum  types— Severity — Eclampsia  without  convulsions 
— Peripheral  nerve  lesions — Blood  pressure  and  its  significance — Role  of  kid- 
neys— Infections — Placental  autolysis — Internal  gland  derangements — Exoph- 
thalmic goiter — Effect  of  thyroidectomy — Mammary  gland  theory — Anaphy- 
lactic  reaction — Dissenting  views  on  sensitization — Prognosis  for  mother  and 
fetus  —  Influence  of  war  diets  —  Differential  diagnosis  —  Epilepsy  —  Chorea  — 
Hysterical  convulsions — Increased  salivation — Presumable  toxemias — Prognosis 
in  toxemia — Literature. 

Introductory. — It  would  be  a  difficult  matter  to  discuss  the 
etiological  factors  underlying  the  production  of  the  so-called  tox- 
emias of  pregnancy  from  any  one  point  of  view,  for,  as  is  now 
well  known,  the  most  divergent  clinical  manifestations  may  be 
accompanied  by  similar  pathological  features,  and,  to  a  certain 
extent,  the  reverse  of  this  also  holds  good.  For  example,  in  the 
disorders  of  the  later  months  of  pregnancy  to  which  the  general 
term  "eclampsia"  is  given,  death  may  be  the  terminal  manifesta- 
tion of  a  series  of  symptoms  marked  by  one  or  more  convulsive 
seizures  and  may  also  constitute  the  final  picture  in  a  case  in 
which  no  convulsions  whatever  occurred.  Autopsies  in  each 
instance  show  practically  the  same  pathological  lesions  in  brain, 
liver,  kidneys,  and  other  organs.  At  first  it  was  believed  that 
abnormalities  of  the  functions  of  liver  and  kidneys  resulted  in 
the  retention  of  certain  by-products  of  body  metabolism  which 
gave  rise  to  a  toxic  state. 

13 


i4  TOXEMIAS  OF  PREGNANCY 

The  earlier  French  observers  particularly  regarded  a  condition 
of  autointoxication  as  present  in  almost  all  pregnancies  and 
attributed  a  large  variety  of  abnormal  manifestations  to  the  same 
process,  including  headache,  skin  eruptions,  salivation,  etc.,  as 
well  as  the  more  serious  manifestations  of  the  eclamptic  seizures. 
Veit  claimed  that  such  disturbances  resulted  from  the  entrance 
of  bits  of  villi  originating  in  the  fetal  ectoderm  which  find  their 
way  into  the  maternal  circulation  and  produce  a  cytolysis.  Ewing, 
Stone,  and  others  believed  that  the  toxemias  of  pregnancy,  includ- 
ing hyperemesis  and  eclampsia,  were  all  evidences  of  disturbed 
metabolism  and  therefore  should  be  regarded  and  treated  as  a 
single  condition  with  varying  manifestations. 

J.  Whitridge  Williams  combats  this  opinion  very  vigorously 
in  his  writings  and  states  that  the  study  of  the  urine  and  blood  as 
well  as  the  histological  examinations  of  tissues  indicates  that 
essential  and  characteristic  differences  exist  between  the  various 
conditions  thus  grouped  together.  He  believes  that  the  prob- 
ability of  the  eventual  discovery  of  their  ultimate  causes  would 
be  greatly  increased  by  considering  them  separately.  Moreover, 
no  specific  poisonous  principles  have  been  isolated  to  date,  nor 
have  any  distinctive  pathological  lesions  been  recognized  which 
could  not  be  associated  with  other  conditions. 

The  classification  of  pregnancy  toxemias  proposed  by  Wil- 
liams is  very  satisfactory  from  the  standpoint  of  our  present 
knowledge  of  the  underlying  chemical  or  physiological  factors, 
although  the  clinical  distinctions  between  nephritic  and  pre-eclamptic 
toxemias,  for  example,  may  perhaps  be  difficult  or  doubtful  in  certain 
cases.  Under  the  general  heading  of  toxemia  of  pregnancy,  Williams 
describes  the  following  groups:  (a)  pernicious  vomiting;  (b)  acute 
yellow  atrophy  of  the  liver;  (c)  nephritic  toxemia;  (d)  pre-eclamptic 
toxemia;  (e)  eclampsia;  (/)  presumable  toxemias.  Adopting  Wil- 
liams' view,  it  will  be  necessary  to  consider  the  etiology  of  each  group 
of  cases  because,  as  already  stated,  later  pathological  studies  seem  to 
point  to  the  necessity  of  dividing  the  various  toxemias  in  this 
manner.  We  must,  however,  still  regard  the  problem  as  unsolved, 
for  notwithstanding  many  theories  that  have  been  put  forward  to 
account  for  any  and  all  of  these  abnormalities,  none  has  been 
satisfactory  enough  to  warrant  its  adoption  as  a  basis  for  definite 
prophylaxis  or  treatment. 


ETIOLOGY  AND  SYMPTOMATOLOGY  15 

HYPEREMESIS  GRAVIDARUM 

Etiology. — Taking  up  first  the  vomiting  of  pregnancy,  it  will 
be  found  to  occur  in  greater  or  less  degree  in  over  one-half  of  the 
cases,  beginning  at  the  end  of  the  first  month  and  continuing 
ordinarily  until  the  third  or  the  fourth  month.  The  appearance 
of  this  symptom  is  so  common  that  the  term  "morning  sickness" 
is  well  known  to  all  pregnant  women.  In  many  instances  nausea 
alone  appears  and  vomiting  is  absent,  or  only  occasional.  The 
gradations  are  numerous  between  this  type  of  vomiting,  which  is 
usually  regarded  merely  as  a  discomfort  and  the  more  serious 
conditions  in  which  the  vomiting  actually  leads  to  starvation,  with 
its  attendant  results.  The  fact  that  nausea  and,  in  many  cases, 
vomiting,  follow  manipulations  on  the  nonpregnant  uterus  (dilata- 
tion of  the  canal  with  gauze,  with  instruments,  or  stem  pessaries) 
makes  it  possible  that  certain  nerve  adjustments  are  needed 
before  the  irritations  from  this  source  no  longer  elicit  reflex  gas- 
tric disturbances.  On  the  other  hand,  a  mere  neurosis  does  not 
serve  as  an  explanation  because  so  many  women  of  a  markedly 
neurotic  type  fail  to  show  any  evidences  of  morning  sickness, 
while  others  who  manifest  no  tendency  in  this  direction  and  are 
apparently  robust  and  calm,  may  suffer  excruciatingly  from  the 
same  symptoms.  Certain  mechanical  displacements  of  the  uterus 
may  be  assumed  to  be  a  causal  factor  in  certain  cases,  as  the 
vomiting  frequently  disappears  when  they  are  corrected. 

Toxic  AND  PSYCHIC  FACTORS. — In  addition  to  the  neurotic  or 
reflex  types,  a  toxic  element  is  most  probably  the  predisposing 
cause  in  the  majority  of  cases  of  hyperemesis;  for  the  symptoms 
often  persist  where  apparently  reflex  causes  have  been  done  away 
with.  One  may  also  assume  that  in  such  cases  the  mental  effect 
resulting  from  the  removal  of  a  mechanical  cause  has  a  marked 
influence  on  the  patient.  In  those  cases  where  there  is  no  true 
toxic  factor,  suggestive  treatment  has  been  employed  on  the 
supposition  that  a  hysterical  element  was  the  underlying  condi- 
tion, and  one  becomes  very  much  impressed  by  this  view  from  the 
fact  that  a  scheme  of  treatment  in  which  absolute  quiet  and  rest 
are  set  down  as  essential  factors,  often  brings  about  a  marked  and 
immediate  improvement  in  the  patient. 

HIGH  AMMONIA  COEFFICIENT. — In  the  large  majority  of  cases, 
however,  it  would  be  better  to  regard  a  toxemia  as  the  true  cause 


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FIG.  i. — GRAPHIC  CHART  SHOWING  URINARY  CONDITIONS  IN  A  CASE  OF  NEUROTIC 
VOMITING  WITH  STARVATION,  CURED  BY  SUGGESTION  AND  FORCED  FEEDING. 
Dotted  line  shows  variations  in  ammonia  coefficient.  Continuous  line  shows  grams 
of  total  nitrogen  (Williams). 


16 


of  the  symptoms,  but  how  can  we  distinguish  the  border-line  cases 
and  determine  whether  we  are  dealing  with  a  true  toxemia  or  a 
reflex  disturbance?  In  the  true  toxemic  cases  there  are  evidences 
of  disturbed  metabolism  in  the  blood  and  urine  upon  which  a 
diagnosis  may  be  based.  Williams  was  the  first  to  show  that  the 
urine  in  such  patients  presents  a  high  ammonia  coefficient,  which 
indicates  that  a  much  larger  proportion  of  the  total  nitrogen  is 
excreted  in  the  form  of  ammonia  than  usual.  Normally  the 
ammonia  coefficient  during  pregnancy  varies  between  4  and  5 
per  cent,  but  in  toxemic  vomiting  it  may  rise  from  20  to  50  per 


A.  No.  2310 
Sept.  14  -  Ocl.  2nd,  1905. 


B.  No.  2519 
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FIG.  2. — GRAPHIC  CHART  SHOWING  AMMONIA  COEFFICIENT  IN  Two  SUCCESSIVE  PREG- 
NANCIES.    A,  toxemic,  and  B,  neurotic  type  of  vomiting  (Williams). 

cent.  These  conditions  are  well  shown  in  the  accompanying 
charts  from  Williams'  textbook  (Figs,  i,  2).  Williams  insists  that 
these  findings  indicate  profound  perversion  of  metabolism  and  are 
associated  with  grave  danger  to  the  patient.  His  statements,  how- 
ever, were  later  contradicted  by  those  who  believe  that  the  high 
ammonia  coefficient  is  a  manifestation  of  acidosis,  or  merely  an 
accompaniment  of  inanition  and  in  no  way  connected  with  a 
toxemic  process.  Williams  claims,  however,  that  the  high 
ammonia  coefficient  in  women  suffering  from  pernicious  vomiting 
is  not  always  susceptible  to  this  explanation,  because  the  employ- 
ment of  soda  bicarbonate  in  his  experience  had  no  effect  upon  the 


iS 


TOXEMIAS  OF  PREGNANCY 


ammonia  coefficient  or  upon  the  reaction  of  the  urine,  which 
would  have  been  materially  altered  in  a 
mere  acidosis.  Williams  also  denies  that  the 
high  ammonia  coefficient  in  all  cases  is  due 
to  inanition,  as  is  clearly  shown  by  the 
history  of  the  patient  whose  urinalysis  is 
presented  in  Fig.  3.  Here  the  ammonia 
coefficient  fell  from  33  per  cent  to  practically 
normal  but  the  inanition  continued  and  he 
explains  this  by  assuming  that  the  high  am- 
monia coefficient  was  a  manifestation  of  a 
toxemia  which  ceased  as  soon  as  the  preg- 
nancy which  caused  it  was  ended. 

Hepatic  Lesions.  —  That  serious  liver 
necrosis  can  be  associated  with  hyperemesis 
was  first  pointed  out  by  Duncan  in  1879 
and  these  observations  were  later  confirmed 
by  Williams,  Stone  and  Ewing,  who  showed 
that  in  some  cases  a  profound  necrosis  of 
the  central  portion  of  the  lobules  took  place 
whereas  the  periphery  remained  intact  (Fig. 
4).  In  place  of  this  necrosis,  marked  fatty 
degeneration  may  occur. 

The  lesions  found  in  the  kidney  in  pa- 
tients dying  from  hyperemesis  show  degen- 
erative changes  in  the  convoluted  tubules, 
including  necrosis  of  the  epithelium.  Wil- 
liams believes  that  the  hepatic  lesions  are 
entirely  different  from  those  observed  in 
eclampsia,  in  which  the  process  begins  in 
the  periportal  spaces  and  is  primarily  due  to 
thrombosis;  that  toxemic  vomiting  is  an 

pIG.  3.— URINARY  CHART  entirely  distinct  process,  and  that  it  has  only 
FROM  A  CASE  OF  TOXEMIC  two  points  in  common  with  eclampsia, 
namely,  that  both  occur  in  pregnant  women 
and  are  manifestations  of  disturbed  meta- 
bolism. He  declares  further  that  it  is  prob- 
able that  the  extensive  destruction  of  liver 
tissue  may  account  for  a  part  of  the  urinary 

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VOMITING.  With  recov- 
ery after  induced  abor- 
tion, showing  total  nitro- 
gen —  continuous  line  — 
and  ammonia  coefficient 
—  dotted  line  (Williams). 


ETIOLOGY   AND   SYMPTOMATOLOGY  19 

metabolism  that  ammonia  and  other  incompletely  oxidized  sub- 
stances are  excreted  instead  of  urea.  He  also  believes  that  when 
the  distortion  of  the  nitrogenous  partition  is  not  due  to  inanition, 
the  greater  part  of  the  change  must  be  attributed  to  the  under- 
lying toxemia  concerning  whose  nature  we  are  not  well  acquainted.1 

The  view  that  the  liver  lesions  are  due  to  chloroform  poison- 
ing was  advanced  by  the  opponents  of  this  theory,  but  Williams 
has  shown  that  the  same  lesions  are  observed  after  the  employ- 
ment of  ether  or  nitrous  oxide  gas,  and  even  in  patients  who  died 
before  any  attempt  at  abortion  had  been  made.  He  claims  that 
there  is  abundant  evidence  to  prove  that  certain  cases  of  per- 
nicious vomiting  are  due  to  a  toxemia,  which  is  associated  with 
a  high  ammonia  coefficient,  a  marked  reduction  in  the  output  of 
urea,  and  with  profound  degenerative  lesions  of  the  liver  and 
kidneys.  Further,  such  a  condition  usually  terminates  in  death 
unless  the  pregnancy  is  speedily  terminated. 

Glycogen  Deficiency. — Duncan  and  Harding  considered  that 
the  similarity  in  the  symptoms  of  ordinary  hunger  and  hyper- 
emesis  might  account  for  the  periodicity  of  the  vomiting  of 
pregnancy,  and  that  the  cause  lies  in  a  lack  of  glycogen  in  the  liver 
which,  they  claim,  leads  to  a  fatty  infiltration  of  that  organ.  Their 
aim  was  to  correct  the  supposed  deficiency  of  carbohydrates  by 
means  of  a  high  carbohydrate  diet  supplemented  by  glucose  or 
lactose,  further  reference  to  which  may  be  found  in  the  section  on 
treatment. 

ACUTE  YELLOW  ATROPHY  OF  THE  LIVER 

Etiology. — The  etiology  of  acute  yellow  atrophy  of  the  liver 
occurring  in  pregnancy  as  such  is  probably  associated  with  the 
same  series  of  deviations  from  the  normal  which  underlie  the 
other  and  better  known  varieties  of  toxemia  of  pregnancy. 
Whether  to  consider  an  acute  yellow  atrophy  of  the  liver  a  clinical 
entity  or  merely  the  terminal  lesion  in  any  given  case  of  hyper- 
emesis  or  eclampsia  cannot  be  determined  without  a  knowledge 
of  its  etiology.  This  must  be  regarded  as  still  uncertain.  In  some  cases 
a  predisposing  cause  may  be  found,  such  as  pernicious  vomiting, 

1  In  this  connection  it  may  be  noted  that  Mottram  found  that  in  the  pregnancy 
of  ill-nourished  animals  the  liver  became  overloaded  with  fat  just  as  in  certain 
stages  of  ordinary  inanition. 


20  TOXEMIAS   OF   PREGNANCY 

sepsis,  eclampsia,  typhoid  fever,  drug  poisoning,  intestinal  auto- 
intoxication, wasting  illness,  etc.,  to  mention  the  more  commonly 
found  conditions,  but  in  other  cases  there  is  apparently  no  pre- 
vious history  of  this  kind.  Collections  of  cases  of  acute  yellow 
atrophy  of  the  liver  show  that  where  it  is  found  among  women, 
anywhere  from  50  to  60  per  cent  of  these  are  pregnant,  or  have 
recently  been  delivered.  In  this  connection  it  is  important  to  note 
that  jaundice  may  occur  in  pregnancy  as  an  accidental  symptom. 
It  may  be  of  the  catarrhal  variety  or  due  to  cholecystitis  or  chole- 
lithiasis, and  again,  it  may  be  of  an  idiopathic  type  in  which  all 
other  etiological  factors  have  been  eliminated.  In  the  latter 
instance  we  are  dealing  merely  with  a  symptom  complex  marked 
by  discoloration  of  the  skin  and  sclera,  by  itching'  and  nervous 
irritability.  One  of  the  characteristic  features  of  this  condition 
is  its  recurrence  in  the  same  or  successive  pregnancies.  The  cause 
of  this  form  of  pregnancy  icterus  has  not  been  determined,  but 
in  view  of  the  known  effect  on  the  liver  cells  of  the  toxins  of  preg- 
nancy we  may  assume  this  to  be  one,  if  not  the  principal,  etio- 
logical factor. 

Differential  Diagnosis. — But  the  symptom  complex  just  de- 
scribed must  be  carefully  distinguished  from  a  true  acute  yellow 
atrophy  of  the  liver,  although  this  may  be  difficult,  for  a  severe 
group  of  symptoms  is  gradually  superimposed  on  the  milder  ones 
of  the  ordinary  jaundice  so  often  seen  in  pregnancy.  Every  case 
of  persistent  icterus  occurring  in  pregnancy  must  be  regarded 
with  apprehension.  Evidences  of  a  more  serious  condition  are  to 
be  found  in  the  nausea  and  vomiting,  more  pronounced  jaundice, 
coated  tongue,  dry  skin,  periods  of  depression  alternating  with 
delirium,  and  convulsive  movements,  usually  of  the  extremities. 
Palpation  shows  a  steadily  enlarging,  tender  liver.  Purpuric  skin 
spots  and  the  finding  of  leucin  and  tyrosin  crystals  in  the  urine 
usually  precede  the  fatal  issue.  It  may  be  difficult  to  draw  a  close 
clinical  distinction  between  an  actual  acute  yellow  atrophy  and 
hyperernesis,  as  marked  degrees  of  jaundice  often  accompany  the 
latter,  but,  while  emptying  the  uterus  often  stops  the  vomiting,  it 
has  no  effect  on  a  true  liver  atrophy.  It  is  probable,  moreover, 
that  many  deaths  from  hyperernesis  are  really  due  to  true  atrophy 
of  the  liver  which  could  be  proved  if  autopsies  were  possible. 

Bacterial  Theory. — In  addition  to  the  predisposing  causes 
already  noted,  the  disease  has  been  attributed  to  a  bacterial  origin, 


ETIOLOGY  AND   SYMPTOMATOLOGY  21 

both  the  streptococcus  and  colon  bacillus  having  been  isolated 
from  the  liver  at  autopsy.  It  has  not  been  shown,  however,  that 
these  are  not  secondary  reinfections  and  the  picture  afforded  by 
sections  of  the  affected  organ  points  to  a  degenerative  rather  than 
an  inflammatory  process. 

NEPHRITIC  TOXEMIA 

The  overburdening  of  the  maternal  kidney  function  during 
pregnancy  undoubtedly  serves  as  a  starting-point  for  the  fre- 
quent disorder  to  which  the  term  "kidney  of  pregnancy"  has  been 
applied.  In  many  instances  an  existing  nephritis  that  can  be 
traced  to  one  of  the  exanthemata  may  undergo  an  exacerbation 
after  years  of  quiescence.  Every  infectious  disease  may  be  com- 
plicated by  nephritis  during  pregnancy  and  the  prevalence  of 
epidemic  influenza  during  recent  years,  I  believe,  accounts  for  the 
increased  number  of  the  cases  that  have  occurred  lately.  The 
presence  of  a  chronic  nephritis  may  be  unknown  to  the  patient 
and  may  make  itself  evident  only  during  pregnancy,  because  of 
the  increased  burden  placed  upon  the  kidneys.  The  mere  pres- 
ence of  albumin  in  the  urine  is  not  necessarily  an  indication  of 
this  lesion,  as  this  may  appear  in  minute  quantities  in  the  urine 
of  perfectly  healthy  people  and  especially  after  severe  exercise, 
butalbuminuria  characterized  by  more  marked  traces  is  associated 
with  many  pregnancies  and  constitutes  a  predisposing  factor  for 
a  more  serious  involvement  of  the  kidneys.  In  all  cases  where  the 
albumen  reaction  averages  i  to  1,000,  or  more,  we  may  assume 
that  the  normal  limits  have  been  exceeded,  especially  if  this  is 
accompanied  by  casts  of  the  hyaline  or  granular  variety. 

Symptoms. — We  find  that  the  onset  of  nephritic  toxemia  is 
gradual  in  most  instances,  which  serves  to  distinguish  it  from  the 
renal  symptoms  in  actual  eclampsia.  Appearing  usually  in  the 
second  half  of  pregnancy,  it  attacks  primiparse  more  often  than 
multipart ;  it  is  also  likely  to  be  associated  with  multiple  preg- 
nancies. In  addition  to  the  urinary  findings,  edema  of  the  ankles 
and  legs  is  present  in  varying  degrees  and  sometimes  involves 
the  lower  portion  of  the  abdomen.  Puffiness  and  swelling  of  the 
hands  is  usually  noted,  although  they  may  not  be  so  evident  as  an 
edema.  In  a  certain  number  of  cases,  headache,  nausea,  indiges- 
tion and  slight  visual  disturbances  are  present. 


22  TOXEMIAS  OF  PREGNANCY 

It  may  be  safely  assumed  that  some  direct  and  specific  toxic 
factor  is  the  exciting  cause  of  this  disturbance  in  the  kidneys  and 
not,  as  was  formerly  believed,  a  mechanical  condition,  such  as  that 
arising  from  increased  intra-abdominal  tension,  heightened  blood 
pressure  or  added  muscular  activity  during  labor.  Functional 
kidney  tests  seem  to  show  that  in  these  cases  the  excretory  pos- 
sibilities for  water  and  salt  are  considerably  reduced.  This  would 
point  to  a  retention  of  these  materials  in  the  organism  with  con- 
sequent ill  effects.  In  many  cases  the  progress  of  the  kidney 
involvement  is  apparently  halted  at  this  stage  and  no  further 
extension  of  the  process  results.  In  others  the  incidence  of  more 
advanced  toxic  symptoms  indicates  an  extension  of  the  process 
clinically  into  a  pre-eclamptic  toxemia  or  into  an  actual  eclampsia. 

There  is  another  group  of  phenomena  to  which  attention  must 
be  called.  Williams,  among  others,  has  pointed  out  that  women 
who  give  birth  to  premature  infants  repeatedly  are  likely  to  be 
the  subjects  of  this  condition.  It  will  be  noted  in  these  cases  that 
the  patient  is  apparently  well  up  to  the  middle  of  her  pregnancy, 
when  albuminuria,  with  an  accompanying  edema,  appears.  The 
patient  goes  into  labor  and  gives  birth  to  a  poorly  nourished 
infant  or  one  that  is  stillborn.  The  children  are  poorly  nour- 
ished because  of  the  insufficient  placental  nutrition,  the  organ  in 
these  cases  being  diseased  and  the  seat  of  infarcts. 

PRE-ECLAMPTIC  TOXEMIA 

It  may  be  difficult  to  draw  a  distinction  between  nephritic 
toxemia  and  that  to  which  the  term  "pre-eclamptic  toxemia"  has 
been  given  and  most  cases  are  probably  better  labeled  by  the 
latter  term.  The  clinical  signs  and  symptoms  show  a  marked 
resemblance  to  that  class  in  which  the  kidney  alone  seems  to  play 
a  leading  part.  A  distinction  may  be  made,  however,  in  that  the 
evidences  of  specific  kidney  lesions  are  less  well  defined  and  we 
may  have  presented  simply  the  picture  of  a  toxic  disturbance. 
Pre-eclamptic  toxemia  usually  comes  on  between  the  seventh  and 
ninth  month  and  may  be  associated  with  a  varied  train  of  symp- 
toms. The  milder  cases  are  characterized  by  headache,  malaise, 
a  moderately  high  blood-pressure  and  more  or  less  edema  of  the 
extremities.  In  the  more  severe  cases  pain  in  the  epigastrium, 
persistent  headache  and  visual  disturbances  (including  spots 


ETIOLOGY  AND  SYMPTOMATOLOGY  23 

before  the  eyes,  inability  to  read,  or  attacks  of  dizziness),  are 
present.  In  some  cases  the  patients  suddenly  find  themselves 
unable  to  see  and  in  other  cases  the  loss  of  sight  may  come  about 
more  gradually.  Mental  disturbances  are  also  frequent  and  the 
patient  may  present  various  types,  ranging  from  irritability  to  a 
state  which  closely  resembles  insanity.  In  some  cases  sleepless- 
ness is  complained  of,  in  others  the  patients  are  drowsy  and  stupid 
most  of  the  time.  Where  the  symptoms  are  not  checked  the  con- 
dition may  pass  into  eclampsia  marked  either  by  convulsions  or  a 
profound  coma  ending  in  death.  A  characteristic  feature  of  this 
condition  is  the  reduction  in  the  amount  of  urine,  which  may  be  as 
low  as  ten  to  fifteen  ounces  in  twenty-four  hours,  containing 
albumen,  casts,  and  sometimes  blood  cells.  As  a  rule  the  urine  is 
highly  acid,  and  acetone  and  diacetic  acid  may  be  present, 
although  less  marked  than  in  other  toxic  manifestations. 

ECLAMPSIA 

Definition. — This  term,  as  now  employed,  is  limited  to  those 
acute  manifestations  of  toxemia  during  the  latter  half  of  preg- 
nancy, characterized  usually  by  convulsive  seizures  after  or 
between  which  there  is  a  loss  of  consciousness.  Recovery  may 
follow  one  or  more  convulsions,  or  a  state  of  coma  ensues  which, 
with  other  manifestations,  may  terminate  in  death.  The  term 
"eclampsia"  is  in  a  sense  a  misnomer,  because  we  find  in  some 
instances  that  coma  and  death  ensue  without  previous  convul- 
sions. As  eclampsia  constitutes  one  of  the  most  serious  complica- 
tions of  pregnancy  a  great  deal  of  time  and  effort  has  been 
devoted  to  studies  directed  toward  the  solution  of  its  cause  or 
causes.  A  glance  at  the  historical  review  will  demonstrate  that 
its  character  was  known  before  the  highly  developed  laboratory 
methods  of  the  present  day  afforded  more  definite  clues  as  to  its 
etiology.  Nevertheless  the  search  must  go  on,  and  it  is  imma- 
terial whether  the  clinician  or  the  laboratory  worker  is  successful. 
The  predisposing  causes,  however,  are  now  better  understood  and 
much  has  been  accomplished  by  prophylactic  measures  in 
reducing  the  incidence  and  mortality  of  eclampsia. 

Frequency. — The  frequency  of  the  occurrence  of  eclampsia 
has  been  variously  estimated.  Statistics  derived  from  maternity 
hospitals  show  a  considerable  variation.  Thus  a  report  by 


24 

Williams  in  1912,  based  on  his  service  at  the  Johns  Hopkins  He  > 
pital,  shows  an  incidence  of  i  per  cent  in  a  series  of  11,000  labors; 
Lichtenstein,  of  Leipzig,  in  1911,  reports  400  cases  of  eclampsia 
in  about  15,000  labors,  or  over  2.5  per  cent.  Reinburg,  presenting 
a  series  of  French  statistics  in  his  thesis,  dated  1905,  found  an 
incidence  of  0.34  per  cent  in  a  series  of  over  26,000  cases.  Finally, 
McPherson  reports  in  a  recent  unpublished  communication,  an 
occurrence  of  890  eclampsias  in  120,000  labors  at  the  New  York 
Lying-in  Hospital,  or  a  proportion  of  about  i  to  135  patients,  or 
about  0.74  per  cent.  In  presenting  statistics  based  on  hospital 
records  it  must  be  borne  in  mind,  however,  that  they  may  be 
unduly  exaggerated  because  of  the  large  number  of  such  patients 
that  are  necessarily  referred  to  institutions  for  treatment. 

Who  Affected  and  Time. — Primiparge  are  more  apt  to  be 
affected  by  eclampsia  than  multipart,  and  both  multiple  preg- 
nancies and  hydramnios  are  generally  assumed  to  be  predisposing 
factors.  Although  associated,  as  a  rule,  with  the  later  months  of 
the  pregnant  period,  cases  have  been  repeatedly  observed  during 
the  first  half  of  pregnancy.  In  one  instance  a  fatal  case  with  con- 
vulsions was  noted  during  the  fourth  month  in  which  the  autopsy 
showed  rupture,  cerebral  hemorrhage  and  a  chronic  nephritis, 
together  with  characteristic  changes  in  the  liver.  E.  P.  Watson 
also  reports  a  case  in  a  primipara  twenty-five  years  of  age  who 
developed  a  gradual  generalized  edema,  headache,  and  finally 
sudden  coma  following  severe  typical  eclamptic  convulsions  at  the 
fifth  month.  The  urine  boiled  solid  and  contained  granular  casts. 
Vaginal  section  was  done  and  twins  delivered.  Postpartum  con- 
vulsions followed  and  the  coma  did  not  disappear  for  three  days 
after  delivery.  Hemiplegia  was  present  in  this  case  for  six  days, 
but  the  patient  finally  recovered.  Ebeler,  in  1916,  collected  50 
cases  of  eclampsia  occurring  in  the  first  half  of  pregnancy.  We 
may  find  that  eclampsia  is  associated  with  abnormal  forms  of 
gestation,  including  extra-uterine  pregnancy  and  hydatidiform  mole. 
Ebeler  also  reports  the  occurrence  of  eclampsia  in  a  case  of  ruptured 
extra-uterine  pregnancy  in  which  the  patient,  after  an  amenor- 
rhea  of  eight  weeks,  developed  the  usual  signs  of  sudden  internal 
hemorrhage.  Operation  was  performed  and  a  few  hours  later  a 
slowly  progressing  coma  developed,  followed  by  listlessness  and 
typical  convulsions.  The  urine  showed  a  large  amount  of  albu- 
men, together  with  numerous  glandular  and  hyaline  casts,  and  the 


ETIOLOGY  AND   SYMPTOMATOLOGY 


patient  died  soon  afterwards.     The  same  author  refers  to  three 
similar  cases  which  he  collected  from  the  literature. 

Influence  of  Seasons. — The  influence  of  the  seasons  on  the 
incidence  of  eclampsia  has  several  times  been  advanced  as  a  pos- 
sible factor  in  the  production  of  this  condition.  Cold,  damp,  and 
unsettled  weather,  such  as  is  often  met  with  in  the  vicinity  of  New 
York  during  the  early  spring  months,  is  attended  by  an  increase  in 
the  number  of  eclampsia  cases  admitted  to  the  hospitals.  Harrar 
has  shown  this  in  a  graphic  manner.  The  accompanying  diagram, 


2.000 


JAN  FEB    HAR   APR   MAY  JUNE  JULY  AUG  {SEPT  OCT  NOV   DEC 


/ 


A 


\i 


FIG.  4. — GRAPHIC  CHART  SHOWING  THE  INCIDENCE  OF  ECLAMPSIA  IN  DIFFERENT 
SEASONS.  Based  on  a  series  of  cases  at  the  New  York  Lying-in  Hospital  (Harrar). 
The  line  depicts  the  number  of  cases  per  100  deliveries. 

(Fig.  4),  which  represents  the  cases  of  eclampsia  occurring  in  the 
Lying-in  Hospital  of  New  York  during  a  period  of  ten  years, 
shows  a  steady  increase  in  the  number  beginning  in  February  and 
reaching  its  maximum  in  April.  This  is  followed  by  a  steady 
decline  with  a  minimum  number  of  cases  reported  during  the 
month  of  November.  The  latter  month,  although  usually  cold,  is 
characterized  by  a  low  rainfall.  Others  have  denied  this  connec- 
tion and  claim  that  the  association  is  entirely  accidental.  Statis- 
tics have  also  been  brought  forward  by  Hammerschlag  to  show 
that  the  disease  is  more  prevalent  in  city  than  in  country  districts; 
but  that  the  mortality  is  higher  in  the  country,  probably  because 
of  the  inability  to  provide  early  and  proper  medical  attention. 


26 


TOXEMIAS  OF   PREGNANCY 


Mortality. — The  mortality  of  eclampsia  unfortunately  remains 
high,  being  estimated  at  from  25  to  33  per  cent  and  even  more  for 
the  mother,  and  at  from  33  to  60  per  cent  for  the  child.  In  recent 
years  improvement  in  these  high  mortality  rates  has  been  noted, 
due  unquestionably  to  better  prophylaxis,  a  subject  which  will  be 
discussed  in  the  section  on  treatment.  At  the  New  York  Lying-in 
Hospital  the  mortality  record  for  recent  years,  in  the  in-door 
service,  is  shown  in  the  following  table : 

INDOOR  MORTALITY  RECORD  OF  ECLAMPSIA  CASES 


Year 

Total  Number  of 
Confinements 

Deaths 

Eclampsia 
Deaths 

1910 

2,041      . 

62 

ii 

1911 

2,275 

48 

9 

1912 

2,521 

56 

12 

1913 

2,745 

55 

8 

1914 

3,060 

68 

15 

iQiS 

3,018 

72 

17 

1916 

3,214 

5° 

ii 

1917 

3,186 

57 

8 

1918 

4,010 

75 

8 

1919 

2,707 

54 

ii 

1920 

2,798 

42 

9 

For  this  same  period  the  death  rate  from  eclampsia  in  the 
Greater  City  of  New  York,  taken  from  the  records  of  the  Munici- 
pal Health  Department,  are  as  follows: 

MORTALITY  RECORD  FOR  GREATER  NEW  YORK* 


Year 

Total  Births 

Maternal 
Deaths 

Deaths  from 
Eclampsia 

1912 

135,655 

676 

161 

1913 

135,134 

668 

171 

1914 

140,647 

679 

164 

1915 

141,256 

710 

144 

1916 

137,664 

666 

158 

1917 

141,564 

651 

169 

1918 

138,046 

664 

184 

1919 

130,377 

644 

171 

1920 

132,856! 

708 

190 

1921 

i34,24if 

746 

169 

*  The  Statistical  reports  of  the  Department  of  Health  of  New  York  City  refer  to  deaths  from  "  con- 
vulsions "  and  "  albuminuria,"  which  are  herewith  considered  to  be  synonymous  with  our  general 
designation  of  eclampsia. 

t  Of  these  6,234  were  stillbirths.  }  Of  these  6,297  were  stillbirths. 

The  hospital  figures  are  high,  because  the  institution  is  quite 
naturally  the  recipient  of  many  cases  originating  outside  its  walls, 


ETIOLOGY  AND   SYMPTOMATOLOGY  27 

but  the  mortality  rate  for  a  large  city  is  large  enough  to  show  the 
serious  character  of  the  disease.  Another  interesting  series  of 
figures  is  presented  by  Dublin,  based  upon  the  records  of  a  large 
life  insurance  company,  in  which  it  is  shown  that  deaths  from 
toxemias  of  pregnancy  are  only  exceeded  by  those  from  "puer- 
peral septicemia,"  and  this  was  confirmed  by  comparison  with  the 
entire  registration  area  of  the  United  States  for  the  years  from 
1910  to  1916. 

The  time  at  which  the  eclamptic  seizure  manifests  itself  varies 
within  wide  limits  according  to  statistics  presented  by  different 
writers.  It  is  generally  assumed  that  the  intrapartum  type  is  the 
most  common,  occurring  in  46  per  cent  of  the  cases,  according  to 
Olshausen;  and  in  61  per  cent,  according  to  Knapp  and  Lichten- 
stein.  Williams  estimates  that  55  per  cent  of  the  cases  are  found 
before  labor  during  the  latter  months  of  pregnancy.  McPherson, 
basing  his  estimate  on  the  statistics  of  the  New  York  Lying-in 
Hospital,  states  that  about  one-third  of  the  cases  occur  post- 
partum.  A  similar  divergence  of  opinion  is  found  in  regard  to  the 
prognosis.  Many  claim  that  the  postpartum  variety  offers  the 
worst  prognosis,  because  the  fetus  and  placenta  as  possible  excit- 
ing factors  have  already  been  eliminated  and  yet  the  toxemia  is 
evidently  severe  enough  to  produce  an  explosion.  Undoubtedly 
the  best  results  attend  the  cases  coming  on  during  labor,  as 
delivery  is  usually  accelerated  by  the  seizures  and  the  cervix  prop- 
erly prepared  for  a  more  rapid  expulsion  of  the  child.  It  is  diffi- 
cult in  any  case  to  estimate  the  outcome,  as  many  women  die  with 
a  history  of  only  a  single  convulsion  and  others  survive  after  a 
great  number.  I  have  had  a  personal  experience  with  a  case  in 
which  recovery,  took  place  after  seventeen  severe  general  con- 
vulsions lasting  over  a  period  of  three  days,  the  patient  making 
a  complete  recovery  with  spontaneous  delivery  of  a  macerated, 
premature  fetus  about  ten  days  after  the  beginning  of  the  attack. 

Clinical  Course. — In  a  typical  case  of  eclampsia  the  symptoms 
are  so  characteristic  that  they  constitute  a  well-marked  clinical 
picture  which  may  be  briefly  described  as  follows:  Premonitory 
symptoms  including  malaise,  headaches,  either  frontal  or  occipital, 
puffiness  of  the  hands,  distinct  edema  of  the  ankles  and  lower 
abdomen,  and  visual  disturbances,  including  spots  before  the  eyes, 
blurred  vision,  and  transitory  attacks  of  blindness,  often  precede 
the  attack  by  varying  periods  of  time.  Immediately  before  the 


28  TOXEMIAS  OF   PREGNANCY 

seizure  we  may  note  irregular  abdominal  pains,  frequently  local- 
ized in  the  epigastrium,  nervousness,  restlessness  and  other  vague 
sensations,  increased  dizziness  and  visual  disturbances. 

In  other  cases,  however,  no  premonitory  symptoms  have 
apparently  been  present,  although  close  questioning,  when 
recovery  has  set  in,  will  often  elicit  the  desired  information.  The 
premonitory  symptoms  noted  may  be  followed  by  a  sudden  gen- 
eral convulsion,  succeeded  by  a  period  of  coma,  or  slight  mus- 
cular twitching,  involving  the  smaller  muscles  of  the  face  and 
hands,  may  be  observed  by  the  patient  herself,  followed  by  a 
general  tonic  or  clonic  convulsion  involving  the  larger  muscular 
groups.  The  patient  throws  herself  about  on  the  bed,  or  may 
sink  to  the  floor;  the  seizure  is  accompanied  by  a  clinching  and 
grinding  of  the  jaws  with  consequent  laceration  of  the  tongue. 
Foaming  at  the  mouth  is  usually  present  and  the  patient  becomes 
markedly  cyanotic.  The  convulsive  movements  then  gradually 
cease  and  the  patient  sinks  into  a  deep  coma  from  which  a  com- 
plete recovery  may  result  before  the  next  convulsion  comes  on,  or 
the  convulsions  may  succeed  each  other  very  rapidly  without  any 
intervening  period  of  lucidity.  The  interval  between  the  con- 
vulsions varies.  If  sedatives  are  administered  as  well  as  other 
treatment,  the  seizures  occur  at  intervals  of  several  hours  or 
sometimes  of  several  days,  but  in  the  more  violent  cases  rapidly 
succeeding  convulsions  without  any  intervening  periods  of  con- 
sciousness may  be  followed  by  early  fatal  termination. 

In  the  majority  of  cases  the  administration  of  sedatives  has  a 
marked  effect  in  reducing  the  number  and  severity  of  the  seizures, 
but  in  certain  instances  nothing  seems  to  check  them,  not  even  the 
emptying  of  the  uterus.  When  the  convulsions  subside  a  hemi- 
plegia  involving  one  or  more  muscular  groups  is  sometimes 
noted  as  the  patient  comes  out  of  the  coma.  If  due  to  hemorrhage 
the  paralysis  remains  a  permanent  one,  or  is  very  slowly  recov- 
ered from,  but  if  produced  by  a  localized  edema  of  the  brain  or  by 
a  very  small  clot,  complete  recovery  rapidly  follows. 

In  cases  where  the  seizure  comes  on  during  the  later  months 
of  pregnancy  and  the  patient  is  not  already  in  labor,  it  may  come 
on  very  quickly  and  one  is  often  surprised  that  primiparous 
patients  with  rigid,  undilated  cervices  undergo  rapid  softening 
and  dilatation  of  the  latter  with  delivery  within  a  period  of  several 
hours.  I  have  observed  in  a  number  of  instances  spontaneous 


ETIOLOGY  AND  SYMPTOMATOLOGY  29 

labor  during  a  slight  attack;  in  other  cases,  as  already  noted, 
recovery  from  the  convulsion  may  result  and  the  patient  may  go 
on  with  her  pregnancy  to  some  later  date  with  a  spontaneous 
delivery  of  a  dead  child,  or,  in  some  instances,  a  living  one.  When 
the  attack  comes  on  during  labor  itself,  rapid  delivery  usually 
occurs  if  no  dystocia  is  present. 

In  Puerperium. — Eclampsia  developing  during  the  puer- 
perium  may  manifest  itself  at  different  periods  after  delivery, 
sometimes  within  a  few  hours,  and  in  some  instances  a  diagnosis- 
of  eclampsia  has  been  made  when  convulsions  come  on  several 
weeks  after  delivery.  We  may  assume,  however,  that  in  such 
cases  the  convulsions  were  due  to  another  cause.  Although  post- 
partum  eclampsia  may  manifest  itself  in  the  form  of  only  one  or 
two  general  seizures,  cases  are  frequently  reported  in  which  the 
condition  is  extremely  severe  with  early  fatal  outcome.  In  most 
of  these  cases  we  have  no  premonitory  warning  symptoms  and 
the  patient,  apparently  well,  suddenly  develops  a  general  tonic 
or  clonic  convulsion  most  unexpectedly.  The  period  of  coma 
which  succeeds  the  convulsion  is  followed  by  recovery  in  which 
the  patient  may  have  no  recollection  whatever  of  the  convulsion 
itself,  and  is  merely  reminded  by  her  lacerated  tongue  of  the  fact 
that  something  was  wrong. 

Without  Convulsions. — Eclampsia  without  convulsions  is  now 
recognized  as  a  distinct  clinical  entity,  since  Schmorl  first  made  a 
report  of  three  such  cases  in  1902.  The  absence  of  the  character- 
istic convulsive  seizures  has  frequently  led  to  some  other  diag- 
nosis, such  as  uremia.  In  these  patients  a  gradually  developing 
coma  may  or  may  not  be  preceded  by  the  aura  described  in  con- 
nection with  the  symptoms  of  an  ordinary  eclamptic  seizure. 
Usually  a  rapidly  developing  coma  is  noted  which  may  last  for 
varying  periods,  or  in  which  the  patient  may  suddenly  expire. 
Autopsy  affords  a  key  to  the  diagnosis  and  we  then  note  the  char- 
acteristic hemorrhagic  and  degenerative  lesions  associated  with 
the  better  known  types  of  the  disease.  In  such  patients  we  often 
find  excessive  hemorrhages  into  the  lateral  ventricles,  or  in  the 
region  of  the  pons,  such  as  are  described  in  the  section  on  pathol- 
ogy, as  having  occurred  in  some  of  the  cases  at  the  New  York 
Lying-in  Hospital. 

Peripheral  Nerve  Lesions. — In  addition  to  the  more  or  less 
permanent  lesions  of  the  central  nervous  system  already  noted  as 


3o  TOXEMIAS  OF  PREGNANCY 

complications  of  the  eclamptic  seizure,  one  may  find  transitory 
involvement  of  various  peripheral  nerve  groups  with  character- 
istic pain,  loss  of  function,  etc.  A  so-called  neuritis  of  this 
type  may  persist  for  many  weeks  after  the  patient  recovers. 
In  some  cases  permanent  mental  derangements  have  been 
noted  with  development  of  a  psychosis  which  is  often  permanent. 
In  every  case  of  insanity  developing  during  the  puerperium  the 
possibility  of  a  toxemia  should  be  borne  in  mind  and  the  treat- 
ment directed  towards  this  possibility.  The  instances  of  hemi- 
anopsia  which  have  been  noted  after  eclampsia  are  undoubtedly 
due  to  central  cerebral  lesions  and  must  be  distinguished  from 
the  permanent  visual  disturbances  due  to  retinal  hemorrhages 
and  separations.  Where  an  edema  of  the  retina  is  present  this 
usually  disappears;  but,  if  hemorrhages  have  occurred,  par- 
ticularly if  they  are  associated  with  marked  nephritis,  recovery 
with  restoration  of  normal  vision  may  be  considerably  delayed. 
Should  the  optic  nerve  be  involved  a  permanent  damage  to  vision 
may  result. 

Blood-pressure. — Increased  blood-pressure  is  generally  re- 
garded as  an  essential  accompaniment  of  various  toxemias  of 
pregnancy,  although  Lynch,  of  San  Francisco,  and  others  have 
shown  that  eclampsia  may  occur  without  such  elevation.  Hyper- 
tension is  accepted  as  a  certain  sign  of  toxemia,  because  arterio- 
sclerosis is  most  uncommon  during  the  child-bearing  age.  A  con- 
stantly increasing  number  of  cases  has  been  reported,  however, 
where  high  blood-pressures  were  not  accompanied  by  evidences 
of  toxemia.  There  does  not  seem  to  be  any  relation  between  the 
amount  of  albumin  in  the  urine  and  the  height  of  the  pressure. 
Lynch  reports  two  cases  of  eclampsia  in  which  no  premonitory 
symptoms  were  present;  in  the  first  of  which  the  highest  pressure 
was  113  during  labor;  in  the  second,  125.  In  the  second  case  con- 
vulsions came  on  two  hours  after  delivery.  The  urine  in  both 
cases  was  negative.  In  a  third  case  of  eclampsia  there  were  no 
convulsions  but  a  deep  coma,  the  highest  pressure  reading  being 
100.  This  case  was  fatal.  Lynch  also  refers  in  this  article  to 
other  cases  gathered  from  the  literature. 

F.  C.  Newell  found  normal  variations  from  100  to  130  in  a 
series  of  150  pregnant  women.  Only  one  patient  within  these 
limits  developed  eclampsia.  He  claims  that  if  the  pressure  is  over 
130  the  patient  should  be  kept  under  close  observation,  even  in 


ETIOLOGY  AND  SYMPTOMATOLOGY  31 

the  absence  of  other  symptoms.  In  this  series  about  II  per  cent 
showed  albumin.  Newell  believes  that  a  temporary  rise  of  blood- 
pressure  may  occur  during  pregnancy  without  the  development 
of  other  symptoms. 

In  connection  with  elevations  of  blood-pressure,  it  is  necessary 
to  take  into  consideration  the  presence  of  other  symptoms  before 
making  a  prognosis.  Edema  of  the  legs,  with  high  pressure,  is 
always  significant,  and  if  the  albumin  is  present,  it  is  dangerous. 
Other  observers  have  repeatedly  confirmed  these  findings,  so  we 
may  rely  on  their  value  as  a  prognostic  indication. 

While  reasonable  limits  should  be  •recognized  for  blood  pres- 
sure readings,  the  individual  patient  must  always  be  considered. 
A  stout,  vigorous,  active,  well-nourished  woman  may  furnish 
readings  of  140  to  150  (systolic)  that  need  not  cause  any  alarm 
if  unaccompanied  by  other  symptoms.  These  figures  in  a  less 
vigorous  patient,  with  possibly  other  attendant  symptoms,  should, 
on  the  contrary,  be  given  due  consideration.  In  some  patients, 
blood  pressure  readings  may  be  abnormally  low,  90  to  1 10  systolic, 
and  here  we  usually  find  other  evidences  of  a  general  asthenia. 

To  avoid  any  possible  extraneous  factors  in  taking  routine 
ante-partum  blood  pressures,  the  patient  should  be  on  the  examin- 
ing table  in  the  prone  position,  with  all  constricting  articles  of 
clothing  loosened.  The  mercury  manometer  is  preferable  to  the 
spring  instrument  for  office  and  bedside  use  and  several  readings 
should  be  taken.  Personally  I  prefer  the  auscultatory  method. 
In  numerous  instances  I  have  seen  the  pressure  drop  20  to  40 
points  after  a  patient  had  lain  on  the  table  for  a  few  minutes  and 
had  her  "nervousness"  relieved  by  reassuring  conversation.  It  is 
advisable  in  such  cases  to  resort  to  means  for  elevating  the  pres- 
sure, and  when  this  has  reached  higher  figures  (120  to  130),  the 
patient  will  be  found  to  be  much  more  comfortable. 

Significance  of. — High  blood-pressure  resulting  in  an  acute 
edema  of  the  brain  has  been  prominently  identified  with  the 
etiology  of  eclamptic  convulsions  by  Zangemeister.  He  insists 
that  the  early  symptoms  are  those  of  pressure,  and  that  the 
measures  which  have  been  successfully  employed  act  by  reducing 
the  edema  and  the  local  irritation.  Labor  pains  raise  the  blood- 
pressure  and  increase  the  cerebral  edema,  according  to  Zange- 
meister, but  venesection  lowers  the  pressure  and  therefore  re- 
duces the  convulsions.  This  author  even  goes  so  far  as  to  advise 


TOXEMIAS  OF  PREGNANCY 


osteoplastic  resection  of  the  skull  in  severe  instances  and  has  actually 
performed  the  operation  in  several  instances  to  which  more 
detailed  reference  will  be  found  in  the  section  on  treatment. 

Urine  in  Eclamptic  Seizure. — An  examination  of  the  urine 
obtained  during  or  just  before  an  eclamptic  seizure  shows  that  it 
contains  high  percentages  of  albumin,  and  in  most  cases  boils 
solid.  Hyaline,  granular  and  often  blood  casts  are  present.  The 


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FIG.  5. — URINARY  CHART  FROM  A  CASE  OF  ECLAMPSIA  WITH  RECOVERY,  SHOWING 
THE  TOTAL  NITROGEN  AMMONIA  AND  ALBUMIN.  The  figures  on  the  right  side 
indicate  the  percentage  of  albumin  and  on  the  left  side  the  grams  of  total  nitrogen 
and  percentage  of  ammonia  nitrogen.  The  total  nitrogen  is  shown  by  the  solid 
black  line,  »the  ammonia  by  the  heavy  dotted  line,  the  albumin  by  the  lower,  more 
lightly  dotted,  line  (Williams). 

specific  gravity  is  high  and  the  acidity  marked.  With  the  sub- 
sidence of  the  seizures  and  the  recovery  of  the  patient,  the  albumin 
rapidly  disappears;  this  offers  a  good  prognosis  for  the  individual 
case  (Fig.  5).  The  finding  of  large  quantities  of  albumin  even 
before  convulsions  is  not  unusual  and  I  have  personally  observed 
cases  in  which  daily  specimens  of  urine  boiled  practically  solid 
and  yet  no  actual  convulsive  seizures  resulted.  There  are  other 
urinary  changes,  including  a  marked  reduction  in  the  amount  of 


33 

nitrogen  and  its  derivatives,  while  creatinin,  amino-acids,  and 
similar  bodies  are  relatively  increased  because  the  total  amount 
of  urine  is  markedly  diminished.  Further  details  of  the  urinary 
findings  in  eclampsia  are  included  in  the  chapter  devoted  to  the 
subject. 

Role  of  Kidneys. — It  is  necessary,  however,  in  considering  the 
etiology,  to  refer  to  the  urinary  organs  themselves  as  possible 
factors  in  the  production  of  eclampsia.  Improper  kidney  function 
was  long  considered  one  of  the  principal  causes  of  eclampsia,  and 
it  is  quite  natural  that  many  of  the  investigations  should  have 
been  directed  to  this  source.  Moreover,  autopsies  show  that  in 
most  cases  the  kidneys  present  undoubted  evidences  of  lesions. 
Whether  the  kidney  lesion  may  be  regarded  as  the  primary  dis- 
turbance and  the  toxemia  a  secondary  phenomenon,  or  whether 
the  reverse  is  the  case,  is  a  matter  that  is  still  undecided.  Many 
authors  insist  that  the  kidney  disturbance  is  the  primary  trouble 
and  that  the  organ  is  either  already  the  subject  of  an  inflammatory 
or  irritant  process,  or  that  its  aberrations  are  due  to  disturbances 
in  the  circulation  from  mechanical  causes.  Pressure  on  the  kid- 
ney or  its  excretory  tube  by  the  growing  uterus  is  believed  to 
be  the  sole  cause  by  some  authors,  who  consider  this  rinding  suf- 
ficient to  recommend  the  emptying  of  the  uterus  as  the  logical 
thing  in  the  treatment  in  order  to  relieve  both  traction  and  com- 
pression. When  the  kidney  yields  readily  to  the  displacing  force, 
the  circulation  is  not  disturbed,  but,  if  the  capsule  is  thick  or  the 
kidney  is  not  freely  movable,  its  blood  supply  is  interfered  with. 
We  may  also  allude  here  to  the  assertions  of  Edebohls  and  his 
followers  that  the  only  relief  in  eclampsia  can  be  secured  by 
operative  stripping  back  of  the  kidney  capsule  in  order  to  permit 
the  restoration  of  its  circulatory  conditions. 

FREQUENCY  OF  RENAL  INFECTION. — The  frequency  of  renal  in- 
fection in  pregnancy,  according  to  Bugbee,  is  not  generally  ap- 
preciated. Although  this  writer  believes  that  the  process  is  hema- 
togenous  in  a  large  percentage  of  cases,  and  that  it  originates  in 
the  colon,  an  important  element  is  lowered  resistance,  or  inter- 
ference with  drainage  due  to  pressure  on  the  ureter  from  the  en- 
larging uterus,  particularly  on  the  right  side,  or  torsion,  stretch- 
ing and  kinking  of  the  tube.  Whether  the  development  of  this 
bacteria  has  anything  to  do  with  the  production  of  eclampsia 
or  a  predisposition  to  it,  or  pregnancy  nephritis,  is  still  an  un- 


34  TOXEMIAS  OF  PREGNANCY 

solved  problem,  but  the  elimination  of  toxic  material  due  to  in- 
testinal putrefaction  through  the  kidneys  must  be  borne  in  mind. 
The  necessity  of  improving  the  drainage  from  the  colon  by  appro- 
priate measures  is  thus  evident.  This  would  mean  a  correspond- 
ing diminution  in  the  number  of  bacteria  passing  through  the 
kidneys  and  of  their  influence  on  these  organs. 

Infections  other  than  Renal. — Infection  of  other  than  renal 
origin  has  often  been  cited  as  an  important  factor  in  the  produc- 
tion of  eclampsia.  Stroganoff  advocated  this  theory  for  the  fol- 
lowing reasons:  Eclampsia  is  a  general  disease  affecting  all 
parenchymatous  organs;  it  resembles  an  acute  infection  by  begin- 
ning explosively  or  after  a  prodromal  stage;  it  is  accompanied  by 
fever;  one  attack  confers  immunity  (  ?)  ;  it  seems  to  have  an  epi- 
demic form.  In  support  of  his  views  Stroganoff  describes  126 
cases  (lo'occurring  in  the  early  months  of  pregnancy),  in  which, 
after  the  cessation  of  the  eclamptic  seizures,  the  pregnancy  con- 
tinued to  a  normal  termination.  La  Vake  later  took  up  another 
aspect  of  the  subject.  He  refers  to  the  view  of  Young  of  Edin- 
burgh, more  fully  discussed  on  a  later  page,  that  pregnancy  tox- 
emia is  due  primarily  to  placental  infarcts  caused  by  thrombosis 
of  the  uterine  vessels,  and  holds,  furthermore,  that  the  cause  of 
the  thrombosis  of  the  vessels  is  an  infection  from  some  primary 
focus.  La  Vake  draws  a  parallel  between  nephritis  following  a 
chronic  septic  condition  and  that  occurring  during  pregnancy, 
and  attempts  to  emphasize  the  resemblance  by  citing  13  case 
reports  in  which  evidences  of  an  infectious  condition  were  appar- 
ently present. 

DENTAL  Foci  OF  INFECTION. — No  attempt  has  been  made  to 
isolate  a  specific  organism  in  explaining  the  possibly  infectious  char- 
acter of  eclampsia,  but  various  sources  for  the  development  of 
such  a  process  have  been  described.  Among  others  we  find  an 
interesting  suggestion  by  J.  E.  Talbot,  who  insists  that  the  fun- 
damental cause  of  eclampsia  is  not  to  be  sought  in  the  products 
of  conception.  Prompted  by  the  findings  revealed  by  X-ray 
examinations  of  the  teeth  in  one  of  his  cases  of  eclampsia,  Talbot 
subjected  a  series  of  97  cases  of  toxemia  to  the  X-ray,  and  claims 
to  have  found  evidence  of  chronic  sepsis  in  the  teeth  in  all  with- 
out a  single  exception.  The  fact  that  in  many  cases  there  is  evi- 
dence of  activity  in  dental  pus  pockets  just  preceding  the  occur- 
rence of  toxemia,  or  complicating  it,  and  the  fact  that  the  severity 


ETIOLOGY  AND  SYMPTOMATOLOGY  35 

of  the  symptoms  is  not  generally  proportional  to  the  amount  of 
chronic  sepsis  present,  are  evidences  which  tend  to  show  that 
there  is  a  relationship  between  chronic  sepsis  and  the  incidence 
of  the  disease. 

That  the  presence  of  a  chronic  septic  process  has  a  secondary 
effect  on  the  kidneys  is  well  known.  The  toxins  of  acute  infec- 
tion produce  an  inflammatory  reaction  in  the  kidneys  with  an 
inhibition  of  their  excretory  functions.  This  reduces  normal 
elimination.  Talbot,  therefore,  considers  it  a  reasonable  hypoth- 
esis to  assume  that  the  symptoms  of  the  toxemia  of  pregnancy 
are  caused  by  the  retention  of  the  normal  physiological  waste 
products  of  the  developing  pregnancy,  this  retention  being  due 
to  the  damaged  functional  power  of  the  kidneys,  which  damage 
has  been  brought  about  by  the  toxins  of  chronic  sepsis  in  the 
blood.  A  vicious  circle  is  thus  established.  The  toxins  of  chronic 
sepsis,  by  their  inhibition  of  the  kidney  function,  cause  a  reten- 
tion of  the  normal  waste  products  of  the  body.  These  waste 
products  are  also  injurious  to  the  excretory  function  of  the  kid- 
neys when  they  are  present  in  abnormal  concentration  in  the 
blood.  Nature's  endeavor  to  improve  this  situation  is  reflected 
in  the  rise  in  blood-pressure,  and  this  is  now  accepted  as  the 
earliest  evidence  of  the  presence  of  toxemia.  Many  cases  are  on 
record  in  dental  literature,  as  well  as  in  medical  writings,  which 
demonstrate  the  good  results  obtained  in  cases  of  arterial  hyper- 
tension by  removal  of  foci  of  infection  from  the  teeth.  It  has  also 
been  reported  that  certain  cases  of  albuminuria  have  been  cured 
by  the  same  means. 

The  pathological  findings  in  the  liver  and  placenta  may  also 
be  explained  by  the  same  theory  of  septic  infection,  these  local 
lesions  being  due  to  the  presence  of  infarcts.  The  presence  of 
the  latter  as  a  cause  of  placental  separation  is  admitted. 

Early  Autolysis  of  Placenta. — The  reference  in  a  previous 
paragraph  to  the  views  of  J.  Young,  of  Edinburgh,  on  the  rela- 
tionship of  eclampsia  and  accidental  hemorrhage,  calls  for  more 
extended  comment.  As  the  result  of  a  very  complete  anatomical 
experimental  investigation  at  the  Royal  College  of  Physicians 
Laboratory  in  Edinburgh,  Young  summarized  his  work  by  the 
statement  that  eclampsia  and  the  albuminuria  of  pregnancy  are 
due  to  the  liberation  of  the  products  of  early  autolysis  of  the 
placenta.  He  has  attempted  to  establish  this  theory  by  the  fol- 


36  TOXEMIAS  OF  PREGNANCY 

lowing  considerations:  (i)  The  toxemias  are  especially  associated 
with  recent  infarction  of  the  placenta.  In  severe  cases  ending 
rapidly  in  labor  there  may  be  no  visible  evidence  of  placental 
disease,  but  if  the  placenta  is  born  several  days  after  the  attack, 
massive  necrosis  may  be  seen.  (2)  Placental  infarction  is  due  to 
an  interference  with  the  maternal  blood  supply  of  the  part.  He 
believes  that  it  can  be  shown  conclusively  that  the  chorionic  ele- 
ments are  dependent  upon  the  maternal  blood  supply  and  can 
live  so  long  as  this  is  retained,  even  if  there  is  no  fetal  supply. 
(3)  Interference  with  the  blood  supply,  which  was  responsible  for 
the  infarction,  is  not  dependent  upon  a  toxic  state  and  may 
occur  in  the  most  extreme  form  where  there  is  no  evidence  of 
a  toxemia,  for  example,  accidental  hemorrhage.  (4)  The  placenta 
is  so  constructed  that,  if  part  of  it  die,  the  products  liberated 
from  the  dying  patch  can  pass  directly  into  the  blood  stream 
(Figs.  6,  7,  8,  9).  In  order,  therefore,  to  establish  a  toxemia 
a  circulation  of  blood  surrounding  the  poison-generating  foci  is 
necessary.  This  explains  the  cessation  of  symptoms  with  the 
death  of  the  child  and  separation  of  the  placenta,  and  also  ex- 
plains the  absence  of  toxemia  in  cases  of  accidental  hemorrhage 
in  which  the  placenta  is  completely  detached  by  the  blood  clot 
or  by  other  means.  The  cases  of  accidental  hemorrhage  asso- 
ciated with  a  toxemia  are  those  in  which  part  of  tjie  placenta 
remains  attached  for  some  time.  The  necrosis  in  this  part  liber- 
ates toxic  materials.  (5)  Where  the  placental  disease  is  gradual 
in  its  onset  there  is  more  chance  of  the  evolution  of  the  infarcted 
patches.  This  explains  why  in  long-standing  albuminurias  there 
may  be  more  visible  placental  disease  than  in  acute  eclampsia. 
(6)  These  facts  all  suggest  that  the  toxemias  are  due  to  the  auto- 
lytic  products  liberated  in  the  early  stages  of  the  placental  death. 
By  imitating  this  process  which  occurs  in  iijero  it  has  been  possible 
to  isolate  from  the  "nealthy  placenta  a  soluble  material  which  repro- 
duces the  clinical  features  and  morbid  changes  which  are  'especially 
characteristic  of  eclampsia,  including  convulsions,  peripheral  focal 
necrosis  in  the  liver,  and  degenerative  lesions  in  the  kidney,  espe- 
cially located  in  the  convoluted  tubules.  Young  admits,  how- 
ever, that  the  occurrence  of  post-partum  eclampsia  stands  in  the 
way  of  a  complete  adoption  of  his  theory.  He  believes  that  the 
evidence  is  of  sufficient  importance  to  warrant  in  all  such  cases 


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ETIOLOGY  AND   SYMPTOMATOLOGY  41 

a  thorough  exploration  of  the  uterus  for  a  possible  piece  of  re- 
tained placenta. 

Internal  Gland  Function. — The  association  between  eclampsia 
and  disturbed  internal  gland  function  has  been  made  the  subject 
of  many  studies,  and  a  wealth  of  bibliographical  references  show 
how  much  in  favor  these  speculations  have  been  with  students 
of  the  subject.  The  readily  observed  changes  in  the  thyroid  gland 
in  pregnancy  led  long  ago  to  the  thought  of  its  possible  partici- 
pation. Thus  it  has  been  assumed  that  the  failure  of  the  thyroid 
gland  to  become  hypertrophied  during  pregnancy  is  probably  fol- 
lowed by  insufficient  metabolism  and  may  result  in  various  forms 
of  toxemia  of  pregnancy.  Graves'  disease,  by  materially  altering 
the  quantity  and  quality  of  the  thyroid  secretion,  is  believed  to 
have  an  important  influence  upon  metabolic  processes;  therefore, 
if  associated  with  pregnancy,  owing  to  the  increased  metabolism 
incident  to  that  period,  it  becomes  a  grave  complication. 

Opotherapy.— When  there  is  a  failure  of  the  normal  hyper: 
trophy  of  the  thyroid  during  pregnancy,  or  when  there  is  a  dis- 
eased thyroid  (as  in  Graves'  disease),  the  administration  of  thy- 
roid substance,  by  supplying  the  deficiency  of  the  normal  thyroid 
secretion  and  by  diuretic  action,  has  been  claimed  to  improve  a 
faulty  metabolism  and  thus  have  a  favorable  influence  upon  the 
manifestations  of  the  toxemias  of  pregnancy.  George  Gray 
Ward,  Jr.,  found  in  two  cases  that  the  use  of  a  saline  extract  of 
thyroid  proteins  made  from  fresh  normal  human  glands  is  more 
efficient  in  rapidity  and  reliability  of  action  than  the  ordinary 
sheep  thyroid  extract.  The  hypodermic  administration  is  supe- 
rior to  oral  use,  especially  in  cases  of  toxic  vomiting  or  eclampsia. 
In  a  subsequent  paper  Ward  claims  that,  when  there  is  a  high 
ammonia  output,  as  shown  by  the  nitrogen  partition,  thyroid 
administration  is  indicated.  Ward  finally  concludes  that  it  is 
necessary  to  distinguish  two  types  of  toxemia:  (i)  Those  cases 
with  no  Graves'  disease,  but  without  sufficient  thyroid  secretion 
to  promote  the  increased  metabolism  in  the  liver  made  necessary 
by  the  pregnancy,  and  probably  due  to  the  failure  of  the  thyroid 
to  become  hypertrophied.  (2)  Cases  associated  with  Graves'  dis- 
ease, which  condition  usually  causes  serious  disturbance  in  the 
metabolism. 

Exophthalmic  Goiter  in  Pregnancy. — A.  Crotti,  in  an  extended 
review  of  the  subject  of  goiter  and  pregnancy,  states  that  the  coin- 


42  TOXEMIAS   OF   PREGNANCY 

cidence  of  pregnancy  with  exophthalmic  goiter  is  unusual,  and  the 
observation  has  been  made  that  it  is  much  rarer  in  hospital  than 
in  private  practice.  In  the  Seitz  collection  of  112  cases  of  exoph- 
thalmic goiter  there  was  apparently  no  change  in  about  40  per 
cent  of  the  cases,  and  he  states  that  a  small  number  even  showed 
some  improvement  during  pregnancy.  On  the  other  hand,  60  per 
cent  were  made  distinctly  worse  by  gestation.  In  about  one 
fourth  of  these  cases,  the  thyrotoxicosis  was  a  serious  menace 
to  life  and  health;  seven  patients  died.  In  five  cases  therapeutic 
abortion  was  performed  and  in  1 1  cases  premature  labors  oc- 
curred, with  three  miscarriages  and  three  macerated  fetuses.  He 
includes  seven  cases  in  which  thyroidectomy  was  performed  dur- 
ing pregnancy.  Theilhaber  also  found  that  the  majority  of  cases 
of  pregnancy  coincident  with  Graves'  disease  were  made  dis- 
tinctly worse,  and  the  same  conclusion  was  reached  by  Klein- 
wachter  and  Hirst.  The  latter  even  claims  that  this  disease  may 
have  its  origin  in  gestation,  that  it  predisposes  to  uterine  hemor- 
rhage and  may  result  in  the  death  of  the  fetus.  J.  Whitridge 
Williams  believes  that  pregnancy  exerts  a  deleterious  influence 
on  Graves'  disease  and  that  the  tachycardia  is  greatly  increased 
during  this  period.  Crotti  declares  that  women  with  exophthalmic 
goiter  should  not  marry,  and  if  they  marry,  pregnancy  should  be 
avoided. 

Effect  of  Thyroidectomy  on  Pregnancy. — I  have  had  an  op- 
portunity to  observe  a  pregnancy  in  a  patient  in  whom  thyroid- 
ectomy had  been  performed.  This  patient,  age  thirty-two,  primipara, 
gave  a  history  of  thyroid  enlargement  for  which  an  operation 
was  performed  about  one  year  previous  to  her  pregnancy.  The 
latter  was  characterized  by  continued  attacks  of  nausea  and  vom- 
iting, extreme  nervousness,  flushes  and  tachycardia.  The  urine 
was  normal  except  for  a  high  specific  gravity.  In  the  belief  that 
some  of  the  symptoms  might  be  due  to  the  lack  of  thyroid  secre- 
tion, thyroid  extract  was  given  in  small  doses  continuously  but 
no  effect  was  noted.  A  moderate  degree  of  hydramnios  developed 
in  the  latter  months  and  the  patient's  condition  became  very  un- 
comfortable. Towards  the  end  of  the  calculated  term  of  preg- 
nancy evidences  of  kidney  disturbance  appeared,  including  marked 
traces  of  albumin,  granular  and  hyaline  casts.  Attempts  at  in- 
duction of  labor  were  not  very  successful  and  finally  abdominal 
cesarean  section  was  performed  under  gas,  oxygen  and  ether 


ETIOLOGY  AND  SYMPTOMATOLOGY  43 

anesthesia.  The  extraperitoneal  procedure  was  followed  in  view 
of  the  prolonged  labor,  the  frequent  examinations  and  the  pres- 
ence of  a  temperature  of  102°  F.  As  the  uterus  was  being  incised 
it  was  found  to  be  in  a  state  of  tonic  contraction,  aggravated,  no 
doubt,  by  the  administration  of  0.5  cubic  centimeter  of  pituitrin 
before  the  abdomen  was  opened,  and  without  the  knowledge  of 
the  operator.  The  extraction  of  the  fetus  was  rendered  very 
difficult  and  a  stillbirth  resulted.  Some  sloughing  of  the  fascial 
layer  of  the  abdominal  wound  subsequently  occurred,  but  as  soon 
as  this  separated  prompt  healing  resulted.  During  convalescence 
the  headaches  disappeared,  the  urine  increased  in  amount,  and 
the  general  condition  improved.  Three  weeks  later  an  exacerba- 
tion of  the  nephritis  occurred. 

In  a  subsequent  discussion  of  the  above  case  at  a  meeting  of 
the  New  York  Academy  of  Medicine,  Dr.  Harold  C.  Bailey  re- 
marked that  possibly  a  condition  of  hyperthyroidism  rather  than 
hypothyroidism  was  present,  as  hyperthyroidism  had  been  known 
to  persist  as  long  as  eighteen  months  after  the  removal  of  the 
gland.  Another  speaker,  however,  believed  that  the  symptoms 
should  be  ascribed  to  hypothyroidism  and,  although  the  surgeon's 
report  stated  that  sufficient  thyroid  tissue  had  been  left  behind, 
this  was  probably  only  sufficient  for  normal  metabolic  processes. 
As  the  thyroid  during  pregnancy  must  compensate  for  ovarian 
hypofunction  its  glandular  activity  was  insufficient  and  therefore 
was  a  contributing  factor  to  the  patient's  toxemia. 

Pertinent  to  the  subject  is  a  comparatively  recent  clinical  study 
by  L.  F.  Watson  based  on  severe  cases  of  toxic  goiter  with 
exophthalmos  and  9  cases  of  toxic  non-exophthalmic  goiter  oc- 
curring during  pregnancy.  It  is  probable  that  patients  with 
goiter  of  a  brief  duration  ascribe  their  increase  in  symptoms  to 
the  pregnancy  itself,  while  in  reality  the  symptoms  are  due  to  a 
beginning  hyperthyroidism.  In  cases  of  pregnancy,  when  the 
exophthalmic  goiter  is  accompanied  by  symptoms,  an  operation 
is  attended  by  more  danger  than  in  the  nonpregnant  patient,  and 
is  not  considered  advisable  unless  the  goiter  causes  serious  diffi- 
culty in  breathing.  Watson  states  that  he  secured  good  results 
with  quinin  and  urea  injections  made  directly  into  the  gland  in 
order  to  produce  localized  aseptic  necrosis  of  a  portion*  of  the 
hyperplastic  thyroid.  He  believes  his  procedure  is  without  dan- 
ger to  mother  and  child. 


44  TOXEMIAS   OF   PREGNANCY 

In  cases  associated  with  deficient  thyroid  function  and  kidney 
disturbance,  thyroid  may  be  administered  continuously  through- 
out the  gestation  and  should  not  be  stopped  until  delivery  is 
completed.  In  the  presence  of  hyperthyroidism  the  danger  of 
convulsions  is  increased  and  they  may  appear  without  the  presence 
of  albumin  or  casts.  In  such  cases  cesarean  section  affords  the 
best  chance  for  the  patient,  although  Gellhorn  advocates  vaginal 
section  under  spinal  anesthesia.  Induction  of  labor  is  contra-in- 
dicated because  of  its  slowness. 

Thyroid  and  Parathyroid  Opotherapy. — Notwithstanding  the 
claims  for  therapeutic  success  with  the  administration  of  thyroid 
gland  in  eclampsia,  which  are  based  on  the  apparent  connection 
between  abnormalities  of  the  thyroid  secretion  and  the  production 
of  eclampsia,  there  is  no  definite  proof  of  the  thyroid  origin  of 
this  disease.  The  lack  of  proof  in  this  direction  has  called  atten- 
tion to  the  parathyroids  and  their  inadequate  functioning 
which  has  been  assumed  to  be  a  cause  of  eclampsia.  Thus 
Massaglia  states  that  the  parathyroid  theory  of  eclampsia  and 
its  treatment  by  this  gland  have  long  been  advocated,  especially 
by  Italian  writers.  He  reports  experiments  made  on  two  dogs 
from  which  he  removed  the  parathyroid  when  they  were  ten 
weeks  old.  Both  animals  grew  up  apparently  healthy  except  for 
traces  of  albumin  in  the  urine.  When  they  became  gravid  they 
seemed  to  thrive  for  about  two  months  and  then  each  in  turn 
developed  severe  tetany.  The  author  regards  this  experimental 
tetany  as  the  equivalent  of  eclampsia  in  women  and  emphasizes 
the  fact  that  the  tetany  subsided  under  parathyroid  treatment. 
In  both  of  the  animals  the  parathyroid  insufficiency  evidently 
remained  latent  until  roused  by  the  stress  of  the  pregnancy  to 
active  manifestations.  In  the  two  experimental  animals  sub- 
sequent pregnancies  showed  a  similar  tendency  to  tetany, 
although  less  marked  than  at  first.  This  also  responded  to  treat- 
ment and  was  never  apparent  at  any  other  time. 

The  Mammary  Gland  Theory. — Persistent  activity  of  the 
mammary  glands  has  been  assumed  to  be  a  cause  of  eclampsia 
with  such  conviction  that  certain  very  radical  measures  of  treat- 
ment are  based  upon  the  theory.  Sellheim  and  other  German 
writers  even  suggest  the  complete  ablation  of  the  breasts  in  such 
cases.  This  theory  has  its  foundation  in  the  astonishing  clinical 
and  pathological  similarity  between  eclampsia  and  the  so-called 


ETIOLOGY  AND  SYMPTOMATOLOGY  45 

parturient  paresis  or  milk  fever  in  cattle.  This  disease  has  long 
been  recognized  in  veterinary  practice  in  the  Scandinavian  coun- 
tries and  also  in  France.  The  apparent  connection  between  the 
two  disorders  both  clinically  and  pathologically  has  long  been 
admitted.  The  recent  work  of  Healy  and  Kastle  has  again  called 
attention  to  the  subject.  A  very  complete  contribution  to  the 
literature  of  the  mammary  gland  theory  has  also  been  made  by 
Wilson. 

EXPERIMENTAL  CONFIRMATION  OF. — From  experiments  made  in 
cattle,  Healy  and  Kastle  are  of  the  opinion  that  eclampsia  is  due  to  a 
toxin  similar  to  that  of  milk  fever  in  cattle  and  elaborated  by  the 
breast  in  a  similar  manner.  They  believe  that  the  toxin  of  this 
disease  is  developed  in  the  udder  as  the  result  of  its  metabolism 
preceding  normal  milk  production.  The  intense  physiologic 
activity  which  is  suddenly  awakened  in  the  mammary  glands  may 
easily  be  conceived  to  give  rise  to  a  great  variety  of  disintegration 
products  of  varied  chemical  character  which  may  be  absorbed 
into  the  circulation  precisely  as  milk  sugar  is  known  to  return 
into  the  organism  in  this  way  at  the  beginning  of  lactation.  They 
tested  their  hypothesis  by  experiments  with  the  colostrum,  and 
found  that  the  first  colostrum  obtained  from  cows  during  an 
attack  of  parturient  paresis  had  severe  toxic  effects  when  injected 
into  other  animals  in  contrast  to  the  relative  inertness  of  fresh 
milk  or  colostrum  from  normal  cows.  The  post-mortem  and 
microscopical  examinations  of  the  organs  of  guinea-pigs  killed 
after  these  injections  were  presented  to  show  the  same  pathologic 
degeneration  and  changes  as  are  characteristic  of  eclampsia.  The 
authors  applied  this  theory  with  great  success  to  the  therapy  of 
parturient  paresis.  The  udder  is  subjected  to  acute  dilatation  by 
means  of  oxygen  or  sterile  air,  thus  preventing  by  pressure  the 
absorption  of  toxins  and  shutting  off  the  blood  supply  of  the  milk 
glands  until  it  has  the  opportunity  to  resume  its  ordinary 
excretory  activity,  and  thus  keeping  the  harmful  products  out  of 
the  blood  stream. 

CRITICISM  OF  THEORY. — We  find,  however,  that  parturient  paresis 
occurs  almost  entirely  post  partum,  while  eclampsia  shows  no  special 
predilection  for  this  period.  Parturient  paresis  increases  in  fre- 
quency in  direct  ratio  with  increased  power  in  milk  production 
while  no  such  finding  has  been  noted  in  eclampsia.  Sugar  is  an 
almost  constant  ingredient  of  the  urine  of  parturient  paresis,  but 


46  TOXEMIAS  OF  PREGNANCY 

is  rarely  found  in  eclamptic  urine.  It  is  evident,  therefore,  that 
further  study  should  include  a  careful  pathological  and  clinical 
examination  of  parturient  paresis  as  well  as  a  determination  of  the 
toxic  or  nontoxic  character  of  the  colostrum  from  eclamptics.  A 
tentative  trial  should  be  made  in  properly  selected  cases  of 
eclampsia  by  the  treatment  of  air  or  oxygen  injection  in  the 
breasts.  Wilson,  in  his  review  of  the  subject,  collected  29  cases 
of  eclampsia  in  which  attempts  were  made'with  varied  success  to 
limit  absorption  from  the  breasts  in  this  manner. 

However  skeptical  one  may  be  regarding  the  mammary 
theory  of  eclampsia,  the  hypothesis,  as  pointed  out  by  Wilson  in 
his  excellent  review,  is  at  least  sufficiently  plausible  theoretically 
to  be  entitled  to  respectful  consideration.  Most  textbook  authors, 
however,  dismiss  the  subject  with  scant  courtesy,  but  we  may  yet 
be  surprised  by  the  results  of  closer  attention  to  metabolism  in  the 
breasts  as  etiological  factors  in  the  production  of  eclampsia. 

Abstraction  of  Calcium  Salts. — The  abstraction  of  calcium 
salts  from  the  mother  by  the  fetus  as  a  cause  of  eclampsia  has 
been  brought  forward  by  J.  G.  Drennan  and  others.  It  is  generally 
believed  that  a  certain  amount  of  fatty  infiltration  of  the  liver 
cells  around  the  hepatic  veins  is  a  physiological  condition  during 
pregnancy  and  lactation.  Drennan  disagrees  with  this  view.  He 
considers  that  this  fatty  infiltration  is  a  pathological  state  due  to 
the  abstraction  of  calcium  salts  from  the  mother's  blood  by  the 
fetus  in  such  quantity  as  to  deprive  the  mother  of  what  is  required 
to  unite  with  the  fatty  matter  in  her  liver  cells  to  form  lipoids  or 
soluble  fats.  These  fats  would  then  be  conveyed  by  her  circula- 
tion to  be  deposited  in  tissues  normally  the  depots  of  free  fat  or 
kept  as  a  source  of  fat  to  the  fetus.  This  fatty  infiltration  causes 
disturbed  liver  function  with  the  production  of  toxins  from  im- 
perfect protein  digestion  and  the  liver  is  thus  unable  to  function: 
The  prevention  and  treatment  of  this  .condition,  therefore,  con- 
sists in  a  liberal  calcium  diet  and  lessened  protein  food. 

Intermediary  Products. — Oliver,  taking  up  this  question  from 
another  standpoint,  states  that  the  eclamptic  intoxication  results 
from  the  intermediary  products  of  nitrogen  metabolism,  and  not 
from  its  end  products.  It  is  also  due  to  the  retention  of  these 
intermediary  products  in  the  nerve  and  muscle  cells,  because 
there  is  an  insufficiency  of  the  requisite  mineral  substances  cir- 
culating in  the  body  of  the  mother  to  satisfy  her  own  needs  and 


ETIOLOGY  AND  SYMPTOMATOLOGY  47 

those  of  the  fetus.  The  demands  made  by  the  embryonic  tissues 
for  phosphorus  and  calcium  exceed  greatly  that  of  the  adult,  con- 
sequently if  there  is  an  insufficient  amount  of  these  mineral  sub- 
stances in  the  circulating  blood  of  the  mother,  the  latter  must 
suffer.  The  oxidation  of  the  projected  matter  in  the  organism 
takes  place  in  intimate  union  with  the  phosphorus  in  the  living 
cell.  If,  therefore,  from  any  cause  the  phosphorus  content  of  the 
maternal  tissues,  especially  that  of  the  nerve  and  muscle  cells, 
becomes  lowered,  then  the  formation  of  urea  is  hampered  and 
the  intermediary  products  of  nitrogen  metabolism  accumulates  in 
the  nerve  and  muscle  cells.  Independent  of  the  auto-intoxication 
which  thus  results,  the  relative  ratios  of  the  mineral  substances  in 
the  maternal  cells  become  so  altered  that  the  normal  nerve  and 
muscular  reactions  and  irritabilities  have  changed  and  convulsions 
are  readily  induced.  Oliver  claims  that  the  varied  diet  of  to-day 
is  very  deficient  in  phosphorus  and  calcium.  In  the  cereal  grains 
there  is  an  abundant  supply,  but  in  the  white  flour  usually 
employed  there  is  little  or  no  phosphorus  or  lime.  He  thinks  that 
a  prophylaxis  against  eclampsia  demands  that  the  pregnant 
woman's  diet  should  contain  an  abundant  supply  of  the  mineral 
substances. 

Anaphylactic  Reaction. — There  is  another  field  of  considerable 
speculative  interest  in  the  study  of  the  etiology  of  the  disease 
which  deals  with  the  possibility  of  eclampsia  as  an  anaphylactic 
reaction.  Rosenau  and  Anderson  first  suggested  this  idea,  which 
was  afterwards  elaborated  by  several  German  authors.  The  latter 
made  a  series  of  extensive  animal  experiments  from  the  results 
of  which  they  concluded  that  the  mother  undergoes  a  process  of 
sensitization  during  pregnancy  through  the  continuous  absorp- 
tion of  small  quantities  of  fetal  protein  material.  Vertes  en- 
deavored to  show  by  experiments  that  animals  can  be  sensitized 
by  their  own  albumin  and  that  the  symptoms  of  hypersensitive- 
ness  are  practically  identical  with  those  of  eclampsia.  Vertes 
also  stated  that  the  organs  of  the  animals  presented  the  same 
changes  post  mortem  as  are  found  in  organs  of  patients  who  have 
died  of  eclampsia.  He  draws  the  conclusions  that  eclampsia  is 
merely  a  manifestation  of  anaphylactic  shock  due  to  the  absorp- 
tion of  chorionic  villi,  and  that  the  albuminuria  of  pregnancy  is 
not  merely  a  mechanical  disturbance  of  function,  nor  a  chemical 


48  TOXEMIAS  OF   PREGNANCY 

disorder  caused  by  the  excretion  of  the  products  of  fetal  metabo- 
lism, but  is  a  premonitory  stage  of  eclampsia. 

Parenteral  Introduction  of  Complex  Protein.  —  Another 
theory  along  similar  lines  is  advanced  by  Hull  and  Rhodenburg, 
who  claim  that  with  the  exception  of  provocative  injection  and 
bacterial  disease,  pregnancy  is  the  only  condition  in  which  com- 
plex protein  material  is  introduced  into  the  general  circulation 
parenterally.  Ferment-active  homologous  protein  when  intro- 
duced into  the  circulation  induces  extensive  degeneration  of  the 
liver,  but  as  a  rule  only  slight  degeneration  in  the  kidney.  The 
authors  consider  that  these  lesions  in  the  rabbit  are  equivalent  to 
those  seen  in  the  organs  of  eclamptic  human  females.  They  used 
homologous  protein  which  had  been  previously  boiled  in  order  to 
destroy  the  enzymes.  Slight  lesions  in  the  liver  resulted,  but  the 
kidney  was  found  damaged  to  a  more  marked  degree.  Large 
quantities  of  albumin  and  all  varieties  of  casts  were  found  in  the 
urine.  The  animals  died  in  convulsions  and  coma,  reproducing 
the  picture  of  eclampsia  in  the  human. 

Leucin. — Leucin  as  a  product  of  autolysis  produces  after  injec- 
tion a  marked  degeneration  of  the  liver  both  in  rats  and  rabbits. 
Hull  and  Rohdenburg  believe  that  eclampsia  is  developed  in  the 
following  manner:  An  overload  of  fetal  elements  is  thrown  into 
the  circulation,  where  it  is  autolyzed  with  the  formation  of  an 
excess  of  leucin.  This  leucin  injures  the  hepatic  vessels  with  con- 
sequent thrombosis,  cloudy  swelling,  necrosis  and  more  or  less 
complete  autolysis  added  perhaps  also  to  protein  fractions  incom- 
pletely broken  down  by  the  liver. 

Dissenting  Views  on  Sensitization. — The  sensitization  of  the 
mother  against  fetal  proteins  has,  however,  been  widely  com- 
bated, especially  in  experimental  studies  made  by  Johnstone  and 
others.  Falls  and  Bartlett  confirm  the  observation  that  proteins 
prepared  from  the  placenta,  when  introduced  under  the  skin, 
usually  cause  a  local  reaction  in  both  pregnant  and  nonpregnant 
individuals.  They  believe  that  this  reaction  is  not  sufficiently 
well  marked  for  diagnosis,  and  that  it  speaks  against  the  theory 
that  the  pregnant  woman  is  specifically  sensitized  to  placental 
proteins.  The  lack  of  a  general  anaphylactic  reaction  in  such 
cases  likewise  supports  this  view.  Eisenreich  also  tried  to  show 
experimentally,  by  means  of  the  passive  transmission  of  hyper- 
sensitiveness,  that  eclampsia  is  not  an  anaphylactic  phenomenon. 


ETIOLOGY  AND  SYMPTOMATOLOGY  49 

He  sensitized  several  guinea-pigs  by  intraperitoneal  injections 
of  maternal  serum,  and  after  from  twenty-four  to  thirty-six  hours 
he  gave  an  intravenous  re-injection  of  fetal  serum.  Among  50 
guinea-pigs  thus  treated,  41  showed  no  symptoms,  while  the 
others  showed  the  noncharacteristic  pseudo-anaphylactic  symp- 
toms. Guinea-pigs  treated  with  the  serum  of  eclamptic  mothers 
or  their  children  failed  to  show  any  reaction  and  not  a  single 
animal  died  from  shock.  This  observation  seems  to  contradict 
the  theory  that  eclampsia  is  an  anaphylactic  phenomenon.  Eisen- 
reich  also  attempted  to  demonstrate  the  fact  that  the  comple- 
ments in  normal  and  eclamptic  pregnant  women  do  not  support 
the  assumption  that  there  are  any  anaphylactic  relations  between 
mother  and  child.  But  the  complement  experiments  showed  clearly 
that  in  eclamptic  patients  biological  processes  are  taking  place 
that  do  not  occur  in  the  normal  pregnant  woman.  The  comple- 
ment content  of  the  serum  of  a  normal  pregnant  woman  is  prac- 
tically constant,  while  that  of  the  eclamptic  woman  shows  great 
variations,  although  not  uniform  ones. 

Liepmann,  who  has  also  studied  the  relation  between  ana- 
phylaxis  and  eclampsia,  claims  that  eclampsia  usually  attacks 
robust,  well-nourished  women,  whereas  the  weak  and  nervous 
type  are  affected  by  anaphylaxis.  Edema  and  albuminuria  are 
present  in  the  former  while  exanthema  with  fever  are  noted  in  the 
latter.  He  claims  that  if  eclampsia  were  caused  by  an  ingress  of 
foreign  albumin  into  the  maternal  blood  from  the  placenta,  then, 
with  each  succeeding  pregnancy,  the  body  would  become  more 
and  more  sensitive;  that  is,  eclampsia  would  become  more  fre- 
quent in  multipart  than  primiparse.  Observation  shows  that 
the  reverse  is  true,  and  the  author  therefore  concludes  that  the  albu- 
min of  the  placenta  which  passes  into  the  maternal  stream  in 
every  pregnancy  is  not  foreign  albumin.  Eclampsia  and  ana- 
phylaxis have,  therefore,  nothing  in  common,  according  to  Liep- 
mann. 

Prognosis  for  Fetus. — A  final  thought  in  discussing  the  subject 
of  toxemia  must  be  given  to  the  fetus.  The  prognosis  for  the 
fetus  in  eclampsia  is  bad,  because  of  the  asphyxia  produced  during 
the  convulsions,  especially  in  a  premature  infant.  Even  if  born 
alive  and  not  incapacitated  by  a  lack  of  development,  convulsions 
are  not  unusual  during  the  first  twenty-four  hours  and  are  often 
fatal.  But  the  fate  of  the  fetus  in  the  presence  of  other  varieties 


50  TOXEMIAS  OF  PREGNANCY 

of  toxemia  must  also  be  considered.  Hertwig  in  his  textbook  on 
embryology  suggests  that  the  formation  of  monsters  may  be  due 
to  the  presence  in  the  blood  of  the  mother  of  certain  toxic  sub- 
stances, including  alcohol.  He  bases  this  opinion  on  experiments 
in  which  the  developing  egg  in  lower  forms  of  animal  life  under- 
went deviations  from  the  normal  when  subjected  to  the  external 
influences  of  various  poisonous  substances.  These  changes  were 
independent  of  those  produced  by  traumata.  Werber  reported  an 
interesting  series  of  experiments  made  on  certain  fish  eggs  sub- 
jected to  the  influence  of  oxybutyric  acid  and  acetone.  He  found 
that  a  variety  of  defects  in  essential  organs  were  produced,  and 
we  may  reason  by  analogy  that  as  these  compounds  are  known  to 
result  from  faulty  metabolism  in  a  pregnant  woman  a  similar 
effect  may  be  produced  on  the  unborn  child.  No  further  evidence 
has  been  adduced,  but  it  is  well  known  that  abortions  and  pre- 
mature deliveries  may  result  from  the  presence  of  a  diseased 
endometrium  or  an  improperly  functioning  placenta.  Although 
the  theoretical  possibility  exists,  it  seems  to  be  contradicted  by 
the  practical  findings  in  many  cases  of  eclampsia  in  which  the 
child  at  birth  is  free  from  defects  in  development,  although  it 
later  presents  certain  evidences  of  toxemia  which  may  result 
fatally.  The  subject  is  one  deserving  of  more  attention,  and  it  is 
possible  that  further  research  along  these  lines  may  explain  cer- 
tain common  monstrosities,  such  as  hydrocephalus,  congenital 
dystrophy,  etc. 

Errors  of  Metabolism. — The  foregoing  pages  present  by  no 
means  all  the  theories  advanced  to  explain  the  etiology  of  eclamp- 
sia, which  has  been  aptly  termed  the  disease  of  theories.  We  have 
no  definite  proof  that  any  one  of  the  causes  mentioned,  or  any 
group  of  them,  are  at  fault.  We  simply  know  that  a  profound 
intoxication  is  present,  but  whether  from  maternal  or  fetal 
sources  is  yet  undetermined.  For  want  of  a  better  term,  "errors 
of  metabolism,"  offers  a  suitable  designation,  and  we  seem  every 
day  to  gather  more  facts  to  substantiate  in  a  general  way,  the 
assumption  that  such  "errors"  constitute  at  least  one  of  the  lead- 
ing factors  in  the  production  of  the  disease. 

Influence  of  War  Diet. — Interest  therefore  attaches  to  obser- 
vations made  during  the  late  war  on  the  incidence  of  eclampsia  by 
Warnekros  and  other  German  writers  who  noted  reductions  in 
the  number  of  cases  of  eclampsia  in  various  clinics  during  this 


period.  Mayer  attributed  the  change  to  the  reduction  in  the  fre- 
quency of  sexual  contact,  for  he  considers  the  repeated  introduc- 
tion of  spermatozoa  in  the  female  organism  as  a  factor  in  pro- 
ducing'anaphylactic  processes.  But  this  theory  is  regarded  as  far- 
fetched by  his  German  colleagues,  who  attribute  the  lessened 
occurrence  of  eclampsia  to  the  lowered  protein  and  fat  contents  of 
the  war  diet,  which  brought  about  a  reduction  in  the  functional 
hyperactivity  of  the  liver  and  kidneys  so  of  ten 'found  in  the  second 
half  of  pregnancy. 

These  observations  on  war  diet  reduction  seem  to  be  in 
agreement  with  those  made  by  others  in  peace  times,  for  it  has 
often  been  stated  that  eclampsia  is  more  frequent  in  northern 
than  in  southern  countries  and  that  strong,  full-blooded  women 
are  more  frequently  affected  than  those  who  are  thin  and  less 
well-nourished.  The  geographical  differences  are  attributed  to 
variations  in  the  diet — a  greater  amount  of  fat  being  taken  in  the 
northern  and  more  vegetables  in  the  southern,  latitudes.  A 
French  observer,  Lafont,  has  noted  that  in  Algiers  the  wives  of 
the  natives  are  much  less  frequently  afflicted  with  eclampsia  than 
the  wives  of  immigrants,  which  he  explains  by  the  fact  that  the 
natives  eat  more  vegetables  and  the  immigrants  more  salty  foods. 
In  Turkey  eclampsia  is  stated  to  occur  rarely  and  in  one  of  the 
largest  lying-in  hospitals  of  Constantinople  an  average  of  only 
two  cases  a  year  has  been  observed.  It  has  also  frequently  been 
claimed  that  eclampsia  is  more  frequent  during  the  winter  than 
the  summer  months,  which  may  be  assumed  to  be  due  to  the 
influence  of  the  food,  as  more  fat  is  taken  in  the  colder  season 
than  during  the  warmer  period. 

Variations  in  Diet. — It  is  to  be  expected  that  the  clinical  pic- 
ture usually  recognized  as  pregnancy  nephritis,  which  is  fre- 
quently a  forerunner  of  eclampsia  itself,  can  be  favorably 
influenced  through  changes  in  food  stuffs.  For  instance,  War- 
nekros'  report  from  Bumm's  Clinic  in  Berlin,  shows  that  the 
incidence  of  nephritis  during  the  two  war  years  of  1915  and  1916, 
was  about  I  per  cent  of  the  total  number  of  labors,  while  during 
the  four  previous  years  it  had  varied  from  2  to  4  per  cent.  These 
figures  were  confirmed  by  an  examination  of  the  statistics  of  three 
other  large  obstetric  hospitals  in  Berlin.  The  number  of  eclamp- 
tic  cases  showed  a  similar  diminution,  being  I  per  cent  or  less,  in 
each  case  as  compared  with  from  2  to  4  per  cent  during  the  years 


52  TOXEMIAS  OF   PREGNANCY 

before  the  war.  Warnekros  thinks  that  these  observations  indi- 
cate that  there  is  a  marked  relation  between  eclampsia  and  diet, 
and,  therefore,  point  the  way  to  the  prophylactic  treatment  of  the 
disorder. 

Epilepsy  and  Eclampsia,  Differentiation  of. — Before  conclud- 
ing the  description  of  the  etiology  and  symptomatology  of 
eclampsia  it  is  important  to  note  at  this  point  some  other  condi- 
tions in  which  convulsive  attacks  occur.  Thus,  it  is  essential  to 
distinguish  between  epilepsy  and  eclampsia,  for  the  beginning  of 
epilepsy  during  pregnancy  is  serious  in  the  sense  of  a  possible 
later  recurrence  or  persistence  of  the  disease,  while  eclampsia,  if 
recovery  ensues,  means  restoration  to  health  in  most  cases.  On 
the  other  hand,  a  single  epileptic  seizure  is  of  little  consequence, 
while  an  eclamptic  attack  is  much  more  serious  and  dangerous. 
The  points  in  the  differential  diagnosis  between  these  two  condi- 
tions may  be  summarized  as  follows :  The  history  of  a  previous 
seizure  is  usually  to  be  noted  in  epilepsy  at  other  times  than  dur- 
ing the  period  of  gestation,  the  recovery  without  coma  is  rapid, 
there  are  no  urinary  signs  of  toxemia,  the  seizures  extend  over 
prolonged  periods  and  do  not  recur  at  brief  intervals  as  in 
eclampsia,  and  no  pathological  organic  changes  occur. 

Binswanger  and  others  have  pointed  out  the  increased  dis- 
position to  recurrence  of  epilepsy  during  pregnancy  in  women 
who  had  seemed  free  from  the  disease  for  many  years.  This  fact 
must  be  borne  in  mind  in  those  cases  where  convulsions  occur  in 
succeeding  pregnancies.  Positive  urinary  findings  with  respect 
to  albumin  and  casts  are  often  necessary  in  doubtful  cases  before 
a  definite  diagnosis  can  be  made. 

Uremia  and  Eclampsia,  Differentiation  of. — The  presence  of 
uremia  in  the  ordinarily  accepted  sense  during  pregnancy  must 
also  be  taken  into  consideration  in  those  cases  where  coma  with- 
out convulsions  constitutes  the  clinical  picture.  In  certain  cases 
convulsions  may  appear  at  varying  periods  after  the  beginning 
of  the  comatose  state.  The  differential  diagnosis  must  often 
depend  on  the  knowledge  of  a  previously  existing  chronic  inter- 
stitial or  glomerular  nephritis  combined  with  a  reduced  excretion 
of  urine.  As  the  treatment  is  practically  the  same,  the  question 
of  immediate  differential  diagnosis  need  not  be  taken  into  con- 
sideration, although  in  a  true  uremia  the  prognosis  is  necessarily 
bad. 


ETIOLOGY  AND  SYMPTOMATOLOGY  53 

Chorea  and  Eclampsia,  Differentiation  of. — The  occurrence  of 
muscular  spasm  due  to  chorea  frequently  demands  differentiation 
from  such  symptoms  due  to  a  toxic  cause.  The  increasing  fre- 
quency of  this  disturbance,  as  noted  in  medical  literature,  merits 
further  attention.  Chorea  formerly  was  regarded  in  the  same 
category  as  hyperemesis ;  that  is  to  say,  as  a  purely  nervous  dis- 
turbance occurring  during  pregnancy.  It  is  well  known  that  a 
previous  history  of  chorea  is  found  in  most  cases  that  present  this 
symptom  during  pregnancy;  but  it  is  also  an  acknowledged  fact 
that  the  convulsive  seizures  characteristic  of  chorea  may  become 
very  much  aggravated  during  this  period,  and  if  they  are  of  a 
general,  rather  than  a  local,  type,  may  even  become  confused  with 
true  eclampsia.  Experience  has  shown  that  we  must  consider 
severe  cases  of  chorea  in  pregnancy  as  a  separate  entity,  perhaps 
of  a  toxic  character.  We  often  find  associated  with  it  other  evi- 
dences of  a  toxemia,  such  as  albuminuria,  headache,  slight  degrees 
of  jaundice,  high  blood-pressure,  etc.,  so  that  it  may  be  quite  diffi- 
cult to  draw  a  line  of  distinction  between  chorea  and  toxemia  as 
we  ordinarily  know  it. 

Mortality  of  Chorea  in  Pregnancy. — The  mortality  of  the 
severer  cases  of  chorea  is  rather  high,  being  estimated  by  various 
observers  as  ranging  from  17  to  30  per  cent.  In  severe  cases,  the 
progress  is  very  rapid  toward  a  fatal  issue  unless  the  pregnancy  is 
interrupted.  In  many  of  these  cases,  where  the  women  have  had 
several  children,  the  history  of  progressively  worse  attacks  will  be 
noted  in  successive  pregnancies,  and  the  ordinary  methods  of 
treating  chorea,  including  the  administration  of  arsenic,  iron,  or 
the  salicylates,  seem  practically  useless.  Autopsies  performed  in 
fatal  cases  of  chorea  have  shown  practically  the  same  severe 
degenerative  processes  in  the  liver  and  kidneys  as  in  eclampsia, 
although  this  is  denied  by  some  writers.  Thus,  Liepmann  speaks 
of  a  personal  case  in  which  he  noted  cerebral  hyperemia  with 
thrombosis  of  the  longitudinal  sinus,  edema  of  the  dura,  emboli  in 
the  large  and  small  veins,  areas  of  softening  in  the  cord  and 
degenerative  processes  in  the  ganglion  cells  of  the  central  nervous 
system  as  well  as  of  the  peripheral  nerves. 

Symptoms  of  Chorea  in  Pregnancy. — In  severe  cases  of  chorea 
the  convulsive  seizures  become  so  intense  that  they  not  only  inter- 
fere with  the  taking  of  food  but  prevent  sleep;  and,  if  unchecked, 
psychic  disturbances  follow  with  elevations  of  temperature  and 


54  TOXEMIAS  OF  PREGNANCY 

diffuse  eruptions.  Notwithstanding  the  differences  of  opinion  in 
regard  to  the  relation  between  chorea  and  the  toxemias  of  preg- 
nancy, the  analogy  in  the  symptoms  and  the  pathologic  findings 
in  some  of  the  cases  should  lead  one  to  bear  this  relationship  in 
mind  and  to  keep  these  patients  under  close  observation. 

In  a  personal  case,  a  para-ii,  who  gave  a  history  of  mild  chorea 
during  her  first  pregnancy,  showed  an  entire  absence  of  the 
characteristic  movements  during  her  nonpregnant  condition. 
After  the  second  pregnancy  began,  the  choreic  movements 
returned  and  continued  throughout;  being  limited,  however,  to 
one  side  of  the  face,  neck,  and  the  arm.  Labor  was  induced  at 
term  because  the  symptoms  seemed  to  become  a  little  worse. 
This  was  done  successfully,  although  terminated  by  forcepc. 
Within  twenty-four  hours  a  severe  chill  with  considerable  jaun- 
dice, increase  in  the  convulsive  movements  and  general  restless- 
ness was  noted  with  elevations  of  temperature  to  103°  F.  The 
incidence  of  the  symptoms  within  a  few  hours  after  delivery  and 
the  absence  of  definite  evidence  of  infection  seemed  to  point  to 
another  cause  for  the  same.  Examination  of  the  urine  showed 
a  moderate  albumin  reaction,  although  this  could  not  be  ac- 
cepted as  confirmative.  The  moderate  jaundice  lasted  about 
twenty-four  hours  and  then  subsided.  In  contrast  to  this  case 
another  may  be  cited,  which  was  seen  a  few  weeks  previously  at 
the  New  York  Lying-in  Hospital.  The  patient,  a  para-iii,  pre- 
sented rather  extreme  choreic  movements  of  the  entire  right  side, 
for  which  labor  was  induced.  There  was  no  other  disturbance 
present,  and  within  a  few  hours  after  the  delivery  of  a  small, 
poorly-nourished  child,  the  patient's  symptoms  rapidly  disap- 
peared. The  child  was  successfully  nursed.  Chorea  gravidarum 
is  therefore  a  complication  that  must  be  carefully  watched  and  its 
association  with  a  possible  toxemia  kept  in  mind. 

Differentiation  of  Eclampsia  from  Hysterical  and  Cerebral 
Convulsions. — Hysterical  convulsions  may  occur  during  preg- 
nancy as  well  as  at  any  other  time,  but  usually  they  may  be  differ- 
entiated from  the  convulsions  of  a  toxic  character  by  the  absence 
of  urinary  signs,  no  loss  of  consciousness,  and  the  absence  of 
cyanosis  and  no  tendency  to  lacerate  the  tongue.  During  labor, 
moreover,  the  attention  of  the  patient  is  concentrated  on  her  pains 
to  such  an  extent  that  the  hysterical  seizures  often  disappear. 
True  toxemia  may  also  be  present,  and  it  is  always  well  to  exer- 


55 

cise  care  and  judgment  in  making  the  diagnosis,  as  the  more 
serious  condition  is  otherwise  overlooked.  Convulsions  due  to  a 
variety  of  cerebral  lesions  must  also  be  taken  into  account. 
Tumors  of  various  kinds  involving  the  motor  areas  may  produce 
symptoms  that  are  difficult  to  distinguish  from  eclampsia. 

The  various  convulsive  manifestations,  other  than  true 
eclampsia,  that  may  occur  during  pregnancy  are  infrequent,  how- 
ever, when  compared  with  the  large  number  of  cases  of  eclampsia 
ordinarily  observed.  Yet  the  points  we  have  enumerated  in  the 
differential  diagnosis  should  always  be  borne  in  mind  in  order 
that  radical  and  perhaps  unnecessary  measures  of  treatment  may 
not  be  instituted. 

Increased  Salivation. — The  secretion  of  excessive  quantities  of 
saliva  during  pregnancy  has  been  ascribed  to  a  toxemia,  although  a 
neurosis,  for  want  of  a  better  term,  is  often  assumed  as  the  cause. 
Cases  of  increased  salivation  are  apparently  less  frequent  than 
formerly  and  I  have  personally  seen  very  few  that  did  not  depend 
on  some  local  irritating  process  in  the  mouth,  such  as  jagged  teeth 
or  inflammation  of  the  gums.  The  annoyance  promptly  ceased 
with  the  removal  of  this  factor.  In  those  severe  cases  reported 
in  the  literature  as  much  as  one  or  two  pints  of  saliva  have  been 
noted.  Little  response  to  treatment  occurred  unless  a  definite 
toxemia  could  be  established,  when  improvement  followed  elim- 
inatory  and  dietetic  procedures.  Exhaustion  of  the  patient  will 
probably  take  place  in  the  severer  grades  of  the  disturbance  unless 
the  pregnancy  is  terminated. 

In  cases  associated  with  vomiting,  improvement  in  salivation 
may  be  looked  for  with  the  subsidence  of  the  symptoms  of  the 
former,  which  points  to  a  toxic  basis  for  these  particular  cases. 


PRESUMABLE  TOXEMIAS 

Skin  Eruptions. — Before  concluding  this  chapter,  attention 
must  be  directed  to  a  group  of  symptoms  not  infrequently  met 
with  during  pregnancy  that  are  undoubtedly  of  a  toxic  origin  in 
which  skin  eruptions  are  a  characteristic  feature.  These  are 
mainly  of  the  dermatitis  type,  including  various  forms — impetigo, 
herpes,  urticaria,  erythema,  and  pruritus.  These  eruptions  usually 
come  on  without  warning  and  may  be  unaccompanied  by  other 


56  TOXEMIAS  OF   PREGNANCY 

symptoms,  although  questioning-  will  usually  elicit  the  reply  that 
constipation  or  digestive  disturbances  have  been  present.  As  a 
rule  the  eruptions  are  transitory,  although  in  cases  of  impetigo 
they  may  be  very  persistent,  as  in  a  case  of  Dr.  A.  B.  Davis  in  the 
Lying-in  Hospital,  which  presented  on  admission  at  the  seventh 
month  of  pregnancy,  an  extensive  impetigo  involving  the  lower 
abdomen,  legs,  arms,  and  part  of  the  face,  including  the  lips.  The 
woman's  discomfort  was  extreme  because  the  blebs  had  become 
infected.  Fortunately  labor  could  be  induced  by  the  administra- 
tion of  castor  oil,  and  within  a  week  after  the  delivery  the  symp- 
toms had  subsided  almost  completely.  The  administration  of 
serum  from  pregnant  or  nonpregnant  women,  as  well  as  that  of 
animals,  has  been  recommended  for  this  purpose.  Urticaria 
very  frequently  occurs  in  pregnancy  and  varies  from  the  occa- 
sional appearance  of  small  wheats  to  extensive  eruptions  cov- 
ering the  entire  body.  The  eruption  is  usually  found  in  individuals 
who  develop  it  during  the  nonpregnant  periods,  and  in  such  cases 
it  is  rather  difficult  to  manage.  As  foreign  protein  is  supposed 
to  be  the  cause  of  the  disturbance,  if  the  specific  protein  can  be 
determined,  proper  measures  may  be  taken  to  relieve  the  patient. 

PURPURA. — Purpuric  eruptions  are  sometimes  noted  in  pregnancy, 
occurring  either  as  occasional,  isolated  hemorrhagic  spots  in  dif- 
ferent parts  of  the  body,  or  as  a  more  severe  manifestation  asso- 
ciated with  the  advanced  stages  of  pernicious  vomiting  or  eclamp- 
sia. The  former  type  is  transitory,  but  in  the  other  instance,  the 
appearance  of  this  symptom  offers  a  grave  prognosis.  In  such 
eruptions  a  differential  diagnosis  must  be  made  between  hemo- 
philia and  scurvy.  Congenital  hemophilia  is  rarely  transmitted  to 
females,  but  if  there  is  a  familial  tendency,  the  vessel  walls  are 
undoubtedly  more  susceptible  to  the  destructive  action  of  preg- 
nancy toxins.  Scurvy  is,  of  course,  rarely  met  with  among  adults 
in  this  country. 

HERPES. — Localized  eruptions  of  herpes  are  not  unusual,  and 
ordinarily  are  of  the  vesicular  or  small  bullous  type.  The  lips  and 
the  extremities  are  usually  affected,  but  occasionally  the  inter- 
costal areas  become  involved  and  pain  is  annoying.  Intestinal 
derangements  ordinarily  may  be  accepted  as  the  cause,  and  when 
they  are  relieved  the  eruption  generally  subsides. 

PRURITUS. — Pruritus  affecting  particularly  the  genital  regions,  is  a 
frequent  manifestation  in  pregnancy  which,  if  not  due  to  an 


ETIOLOGY  AND  SYMPTOMATOLOGY  57 

evident  local  cause,  may  be  accepted  as  an  evidence  of  toxemia 
which  subsides  when  the  cause  has  been  eliminated. 

URTICARIA. — Urticaria  constitutes  a  very  annoying  and  not  un- 
usual complication  of  pregnancy,  and  may  be  ascribed  to  the 
increased  vasomotor  irritability  during  this  period. 

Angioneurotic  Edema. — This  is  a  condition  that  may  be  dif- 
ficult to  recognize,  as  it  resembles,  if  occurring  in  the  extremities, 
the  ordinary  subcutaneous  edema  so  frequently  found.  The  tran- 
sitory character  of  the  former  is  a  conclusive  feature,  however,  as 
is  the  fact  that  ordinary  edematous  areas  are  not  limited  to  the 
extremities  but  may  occur  in  any  part  of  the  body. 

Prognosis  in  Toxemias  of  Pregnancy. — As  regards  prognosis 
in  the  various  toxemias  of  pregnancy,  a  final  summary  may  be 
introduced  here.  Taking  up  the  different  types  and  beginning 
with  hyperemesis,  we  may  safely  say  that  even  in  moderately  severe 
vomiting,  the  outlook  is  good  so  long  as  what  may  be  called  the  nutri- 
tional balance  is  maintained.  That  is  to  say,  if  no  great  loss  of  body 
weight  results,  if  the  patient  is  able  to  be  up  a  good  part  of  the  day,  and 
the  urine  does  not  show  any  marked  evidences  of  acidosis,  the  final  out- 
come will  usually  be  favorable.  As  a  rule  if  the  ordinary  termina- 
tion of  the  vomiting  period  is  safely  reached  without  abortion,  the 
pregnancy  proceeds  without  any  after  effects  of  the  disturbance  in 
the  succeeding  months.  But  if  incessant  nausea  and  vomiting  is 
accompanied  by  rapid  loss  of  weight  and  strength;  if  the  vomitus 
contains  coffee-ground  material  which  denotes  hemorrhages  from 
mucous  membranes;  if  jaundice,  dry  and  coated  tongue,  and  pros- 
tration are  present;  if  bile  pigments,  albumin,  casts,  leucin  or 
tyrosin,  diacetic  and  oxybutyric  acid  and  acetone  appear  in  a 
urine  of  high  specific  gravity,  then  the  outlook  is  serious,  even 
if  abortion  is  finally  accomplished.  The  possibility  of  the  recur- 
rence of  hyperemesis  in  subsequent  pregnancies  need  not  be  con- 
sidered in  deciding  on  radical  treatment.  I  have  had  several  cases 
in  which  pregnancy  was  interrupted,  which  were  entirely  free 
from  this  complication  in  succeeding  gestations. 

In  the  presence  of  acute  yellow  atrophy  of  the  liver  the  prognosis  is 
invariably  bad,  and  in  nephritic  toxemia  only  a  prompt  response  to 
treatment  should  give  other  than  a  guarded  prognosis.  In  nephritic  as 
well  as  in  pre-eclamptic  toxemia,  temporary  alleviation  of  symptoms 
often  lead  to  false  hopes.  The  prognosis  in  eclampsia  has  already  been 
referred  to,  but  each  individual  case  must  be  carefully  studied  and 


58  TOXEMIAS  OF   PREGNANCY 

the  outcome  based  on  the  subsidence  of  symptoms  or  the  appear- 
ance of  the  numerous  complicating  lesions  already  described. 

Recurrence. — After  the  occurrence  of  severe  toxemia  in  case 
of  recovery,  the  question  is  often  asked  whether  this  complication 
will  recur  in  the  event  of  another  pregnancy.  Siemens  reports  a 
series  of  18  personal  cases  in  which  more  than  one  subsequent 
pregnancy  occurred.  In  those  patients  who  had  suffered  from 
toxemia  in  the  latter  months  of  the  first  pregnancy,  fifteen  had 
albuminuria  only  in  the  first  pregnancy  and  in  subsequent  gesta- 
tions they  were  free  from  the  slightest  symptom  of  toxemia  and 
were  delivered  of  healthy  children.  On  the  other  hand,  three 
suffered  from  this  complication  in  each  pregnancy.  Two  were 
twice  pregnant  and  recovered,  and  the  third  died  of  nephritis 
several  months  after  her  fourth  pregnancy  had  been  terminated 
on  account  of  pronounced  albuminuria.  It  would  seem,  therefore, 
that  out  of  six  women  who  have  suffered  from  albuminuria  in  the 
first  pregnancy,  only  one  may  expect  the  complication  to -reappear. 

HOSPITAL  STATISTICS  AS  TO. — Siemens'  cases  were  all  private  pa- 
tients, but  hospital  statistics  show  a  large  number  of  recurrences. 
Thus,  Le  Page  found  that  21  per  cent  suffered  from  similar  symp- 
toms in  early  pregnancies.  From  the  records  of  the  Johns  Hop- 
kins Hospital,  Williams  reports  about  the  same  proportion  of 
recurrences,  so  that  the  same  prognosis  may  be  assumed. 
Siemens  attempted  to  devise  some  means  by  which  a  possible 
prognosis  could  be  formulated  in  such  cases.  Examination  of  the 
urine  subsequent  to  delivery  should  be  continued  for  some  time 
and  the  estimation  of  the  quantity  of  albumin  is  very  helpful. 
Thus,  if  the  albumin  is  reduced  to  a  faint  trace  in  the  course  of  a 
week,  permanent  damage  to  the  kidney  is  unlikely  and  the  outlook 
for  future  pregnancies  good.  On  the  other  hand,  a  measurable 
amount  of  albumin  persisting  over  six  or  eight  weeks  offers  a 
very  gloomy  prognosis,  even  though  ultimately  it  disappears 
entirely.  In  such  cases  the  kidneys  are  defective  and,  although 
they  may  be  adequate  for  the  requirements  of  health  in  the  inter- 
vals between  pregnancies,  they  begin  to  show  signs  of  strain  after 
the  sixth  month  of  gestation.  Occasionally,  rigid  restrictions 
regarding  diet  and  exercise  serve  to  carry  the  patient  to  a  point  in 
the  pregnancy  where  the  fetus  is  viable;  but  as  a  rule  the  mother 
suffers  from  grave  albuminuria  and  gives  birth  to  a  macerated  or 
immature  fetus. 


ETIOLOGY  AND  SYMPTOMATOLOGY  59 

When  the  disappearance  of  the  albumin  is  less  marked 
but  persists  for  three  or  four  weeks,  the  opinion  as  to  the  ultimate 
prognosis  must  be  more  doubtful.  Some  patients  may  pass 
through  a  pregnancy  free  from  complications,  but  in  others  the 
toxemia  will  reappear.  In  the  latter  group  the  liver  involvement 
must  also  be  taken  into  account.  The  blood-pressure  observa- 
tions in  such  cases  are  of  greater  value  than  the  albumin  estima- 
tion, as  a  prompt  drop  will  occur  where  the  kidneys  are  not 
defective.  Holste  refers  to  an  unusual  case  in  which  the  patient 
was  subject  to  eclamptic  seizures  during  four  successive  years,  the 
last  one  ending  fatally.  Although  the  patient  had  been  under 
constant  supervision  and  prophylactic  treatment,  nevertheless  she 
developed  convulsions.  Operative  delivery  was  necessary  in 
every  case.  Autopsy  showed  extensive  broncho-pneumonia  with 
parenchymatous  degeneration  of  the  heart  muscle  and  the  liver. 
The  kidneys  seemed  relatively  slightly  involved.  In  view  of  the 
predisposition  to  recurrent  eclampsia  in  this  patient,  the  writer 
believes  that  she  should  have  been  sterilized.  Slemons  also  states 
in  his  article  that  he  does  not  consider  that  the  chemical  methods 
for  estimating  the  efficiency  of  the  kidney  have  proved  of  any 
help  in  prognosis ;  in  fact,  it  has  been  found  that  patients  with  a 
grave  toxemia  often  eliminate  the  phenolsulphonephthalein  given 
in  the  functional  test  more  rapidly  than  healthy  persons. 


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SLEMONS,  J.  M.,  Is  Albuminuria  Likely  to  Recur  in  Successive  Preg- 
nancies? Am.  Journ.  Obst.,  1913,  67,  849. 

STOLPER,  L.  Zur  Aetiologie  und  Diagnose  der  Hyperemesis  gravid- 
arum. Gynak.  Rundsch.,  1914,  8,  85. 

TALBOT,  J.  E.  A.  Theory  on  the  Etiology  of  the  Toxemia  of  Preg- 
nancy. Surg.,  Gyn.  and  Obst,  1919,  28,  165. 

VARO,  B.  Rarity  of  Eclampsia  on  War  Diet.  Ref . :  in  Centralbl.  f . 
Gynak.,  Leipz.,  1920,  May  15. 

VERTES.    Monatschr.  f.  Geburtsh.  u.  Gynak.,  Berl.,  1914,  40,  446. 

WARD,  JR.,  GEORGE  GRAY.    Surg.,  Gyn.  and  Obst.,  1912,  Aug. 


62  TOXEMIAS  OF  PREGNANCY 

WARNEKROS.    Centralbl.  f.  Gynak.,  Leipz.,  1916,  46,  Nov. 

WATSON,  L.  F.     Journ.  A.  M.  A.,  1918,  71,  875. 

WERBKR.     Bull.  Johns  Hopkins  Hosp.,  1915,  26,  226. 

WILSON.    Am.  Journ.  Obst,  1913,  67,  mi. 

YOUNG,  J.     Proc.  Roy.  Med.  Loncl.,  1914,  7,  307.     Obst.  Sect. 

YOUNG,  J.,  AND  MILLER,  D.   A.     Etiology  of  Eclampsia  and  Pre- 

eclamptic  State.    Brit.  M.  J.,  1921,  April  2,  486. 
ZANGEMEISTER.    Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1915,  79. 


CHAPTER  III 

PATHOLOGY 

Hyoeremcsis — Hepatic  lesions — Evidences  of  fetal  origin — Renal  lesions — Hemor- 
rhages— Acute  yellow  atrophy — Differentiation  from  jaundice  associated  with 
severe  hyperemesis  and  eclampsia — Nephritic  and  pre-eclamptic  toxemias — 
Functional  renal  tests — Eclampsia — Renal  and  hepatic  lesions — Hemorrhages — 
Cerebral  edema — Ocular  lesions — Placental  infarcts — Other  findings — Con- 
clusions— Literature. 

The  preceding  section,  dealing  with  the  etiology  of  pregnancy 
toxemias,  presents,  it  must  be  admitted  with  regret,  a  picture 
dominated  largely  by  uncertainty  and  speculation.  This  uncer- 
tainty has  been  correspondingly  reflected  in  most  efforts  to  place 
the  pathology  of  these  disorders  on  a  satisfactory  basis  of  estab- 
lished relations  between  cause  and  effect.  After  the  idea  that 
hyperemesis  was  a  reflex  or  neurotic  disturbance  was  dispelled 
by  autopsy  findings  apparently  closely  resembling  the  lesions 
associated  with  eclampsia,  a  considerable  period  of  time  elapsed 
before  the  fact  became  established  that  well-marked  differences 
exist  between  the  pathological  pictures  underlying  the  toxemias 
of  the  earlier  and  the  later  months  of  pregnancy.  The  belief  that 
the  same  or  similar  metabolic  or  other  disturbances  occurring  at 
no  matter  what  period  of  pregnancy,  caused  identical  lesions  in 
the  liver  and  kidneys  was  not  borne  out  by  closer  histological 
study.  J.  W.  Williams,  among  others,  has  pointed  out  differences 
in  the  liver  and.kidney  lesions  at  different  periods  and  I  believe  it 
will  be  less  confusing  to  base  our  consideration  of  the  pathology 
of  pregnancy  toxemias  on  the  clinical  classification  followed  in 
the  previous  section. 

The  development  of  blood  chemistry  studies  in  toxemias  has 
opened  up  an  entirely  new  field  of  research  within  recent  years 
which  is  of  sufficient  importance  to  warrant  its  consideration  in 
a  separate  chapter.  The  urinary  changes  in  pregnancies  thus 
complicated  have  always  occupied  a  great  deal  of  attention,  and 
while  their  study  has  been  somewhat  relegated  to  the  background 

63 


64 


TOXEMIAS  OF   PREGNANCY 


by  the  advent  of  blood  chemistry  investigations,  the  subject  will 
be  given  full  consideration  in  a  separate  chapter. 


HYPEREMESIS 

Hepatic    Lesions.  —  The    pathologic    lesions    in    the    milder 
types  of  hyperemesis  are  quite  unknown  except  as  they  may  be 

F.L.C. 


L.C 


•  ''•'.•:    '..  •V'-'V  "'•','.'•';  ":.'*^V*.%\   V*' 


" 


FIG.  10. — SECTION  OF  LIVER  FROM  A  FATAL  CASE  OF  VOMITING  OF  PREGNANCY  SHOWING 
CENTRAL  NECROSIS.  F,  L,  C,  liver  cells  showing  fatty  degeneration;  L,  C, 
unchanged  liver  cells;  N,  areas  of  necrosis;  P,  5,  portal  space  (Williams). 

interpreted  from  studies  of  the  blood  or  urine.  In  the  cases  with 
fatal  termination,  the  most  characteristic  organic  change  is  to  be 
found  in  the  liver,  which,  first  pointed  out  by  Duncan  in  1879,  was 
later  confirmed  by  Ewing,  Stone  and  Williams  in  this  country, 
and  by  Winter  and  Hofbauer  in  Germany.  The  hepatic  lesion 


PATHOLOGY  65 

resembles  that  found  in  acute  yellow  atrophy,  and  the  most  note- 
worthy and  constant  finding  is  a  necrosis  of  the  central  lobules,  the 
periphery  remaining  intact  (Fig.  10).  In  this  respect  there  is  an 
essential  difference,  as  Williams  and  others  have  pointed  out, 
from  the  hepatic  lesions  associated  with  eclampsia  where  the 
process  begins  in  the  periportal  spaces.  The  reduction  in  the  size 
of  the  liver  and  the  fatty  degeneration  of  the  cells  often  found 
make  it  doubtful  whether  such  cases  should  not  be  regarded  as 
true  acute  yellow  atrophy.  There  is  nothing  specific  about  these 
findings  for  hyperemesis,  although  they  are  usually  associated 
with  the  fatal  cases,  for  similar  lesions  are  found  in  fatal  cases  of 
phosphorus,  arsenic,  chloroform,  and  other  poisonings  by  chem- 
ical substances.  But  these  findings  do  point  to  the  toxic  character 
of  the  disease,  and  in  severe  cases  where  recovery  has  ensued, 
such  lesions  may  at  one  time  have  been  present,  although  recov- 
ery has  obliterated  all  traces  of  their  existence.  We  may 'assume 
their  existence,  however,  from  the  urinary  findings  and  it  is 
possible  that  more  precise  functional  tests  directed  to  the  blood  as 
well  as  to  the  urine  may  reveal  their  presence. 

Evidence  of  Fetal  Origin. — That  the  circulating  poison  in 
hyperemesis,  if  such  it  is,  is  of  fetal  origin  or  stimulus,  is  evidenced 
by  the  fact  that  unless  the  organic  changes  have  advanced  beyond 
the  reparative  point,  almost  immediate  recovery  results  from 
abortion  or  the  death  of  the  fetus.  The  fact  that  cases  have  been 
reported  by  Pick  in  which  vomiting  did  not  cease  until  all  traces 
of  secundines  had  been  removed,  would  seem  to  point  to  the  syn- 
cytial  layer  as  the  source  of  the  poison  and  thus  confirm  Veit's 
theory  of  the  migration  of  the  placental  villi.  This  theory  is  also 
apparently  substantiated  by  the  frequent  association  between 
hydatid  mole  and  pernicious  vomiting.  Pinard  reports  a  true 
hyperemesis  in  19  instances  out  of  27  cases  of  hydatid  mole,  and 
Behm  declared  that  in  any  case,  chorionic  villi  might  find  their 
way  into  the  maternal  circulation  and  result  in  anaphylactic  symp- 
toms. No  satisfactory  histologic  proof,  however,  has  been 
brought  forward  to  substantiate  this  theory. 

Renal  Lesions. — In  addition  to  the  lesions  in  the  liver  of  fatal 
hyperemesis  cases,  more  or  less  extensive  changes  in  the  kidneys, 
ranging  from  a  simple  exudate  to  a  severe  parenchymatous 
nephritis  have  been  found.  In  fact,  cases  have  been  reported  by 
Erisman  in  which  renal  lesions  alone  were  found. 


66  TOXEMIAS  OF   PREGNANCY 

Hemorrhages. — Hemorrhages  into  the  serous  cavities  and 
membranes  have  been  observed  in  isolated  cases  by  Schickele  and 
bleeding  from  the  gastric  mucosa  is  quite  common.  Petechise  in 
the  serious  cases  are  frequently  seen  and  bleeding  between  the 
uterine  wall  and  the  fetal  membranes  is  also  found. 

Interpretation  of  Findings. — An  anatomical  basis  for  hyper- 
emesis  might  pardonably  be  assumed  to  be  established  from  the 
extensive  autopsy  studies  made  by  Williams,  Stone,  Ewing, 
Hirschberg,  Marchand,  Beatty  and  othsrs,  but  Heinrichsdorf 
insists  that  these  findings  are  not  due  to  pregnancy  toxemia,  be- 
cause of  the  prolonged  course  of  the  hyperemesis  and  the  acute 
character  of  the  organic  lesions.  He  also  claims  that  a  similar 
pathologic  picture  is  found  in  cases  without  any  previous  hyper- 
emesis. In  other  words,  an  acute  yellow  atrophy  of  the  liver  is 
merely  a  complication  of  the  toxemia  and  not  a  primary  lesion 
preceding  the  latter.  It  seems  reasonable  to  believe,  however, 
that  a  common  toxin  underlies  the  hyperemesis  and  the  later 
degenerative  processes  in  the  liver. 


ACUTE  YELLOW  ATROPHY  OF  THE  LIVER 

Hepatic  and  Renal  Lesions. — The  pathologic  picture  to  which 
this  appellation  has  been  given  is  confusing,  but  it  undoubtedly  is 
the  terminal  lesion  in  many  fatal  cases  of  toxemia  which  are 
ordinarily  designated  as  hyperemesis  or  eclampsia.  Preceded  by 
jaundice,  with  or  without  other  symptoms,  the  liver  becomes 
tender  and  diminishes  daily  in  size.  This  is  accompanied  by 
ecchymoses  and  the  appearance  of  leucin  and  tyrosin  crystals  in 
the  urine.  The  autopsy  shows  intense  yellow  staining  of  the  body 
tissues  and  the  liver  may  be  only  half  it's  usual  size.  Marked  fatty 
degeneration  and  necrosis  of  the  hepatic  cells  is  found  in  micro- 
scopic sections,  especially  of  the  central  portions  of  the  acini;  in 
other  words,  an  acute  parenchymatous  hepatitis.  Degenerative 
processes  are  also  present  in  the  kidneys,  involving  the  epithelial 
cells  of  the  convoluted  tubules,  while  the  glomerular  structures  are 
but  slightly  changed. 

Differentiation. — The  pathological  diagnosis  in  well-devel- 
oped, typical  cases  of  acute  yellow  atrophy  is  sharply  marked,  but 
in  both  hyperemesis  and  eclampsia,  when  jaundice  appears  and  is 


PATHOLOGY 


67 


associated  with  the  presence  of  leucin  or  tyrosin  in  the  urine,  the 
differentiation  may  be  difficult  and  can  only  be  determined  by  the 
autopsy.  In  eclampsia  the  liver  changes,  according  to  Heinrichs- 
dorf  and  others,  are  focal,  because  they  are  believed  to  be  due  to 
thrombosis  of  the  minute  interlobular  vessels  and  the  peripheral 
capillaries,  while  in  acute  yellow  atrophy  the  fatty  degeneration 


FIG.  ii. — SECTION  OF  LIVER  FROM  A  CASE  OF  ACUTE  YELLOW  ATROPHY,  SHOWING 
DESTRUCTION  OF  ALL  BUT  A  FEW  GROUPS  OF  LIVER  CELLS  (Ewing). 

and  necrosis  are  diffuse.  Moreover,  a  diminution  in  the  size  of 
the  liver  is  not  associated  with  either  pernicious  vomiting  or 
eclampsia,  although  Heinrichsdorf  asserts  that  the  former  is 
merely  a  rudimentary  kind  of  acute  yellow  atrophy. 

The  clinical  picture  of  hepatic  degeneration  is  so  constant  in 
toxemias  of  pregnancy  that  we  may  refer  at  this  point  to  a  classi- 
fication proposed  by  Seitz  in  which  the  gross  pathological  changes 
in  the  liver  are  differentiated  as  follows: 


68 


TOXEMIAS   OF   PREGNANCY 


1.  Toxic  degeneration,  characterized  by  diffuse  fatty  infiltration 
of  the  liver  cells,  without  marked  generalized  necrosis  and  without 
contraction    in    the   sixe   of   the   organ,   with   a   clinical   picture  of 
hyperemesis  or  general  intoxication. 

2.  Acute  yellow  atrophy,  marked  by  diffuse  fatty  degeneration 
with   extensive   necrosis   and   reduction  in   the   size  of  the  liver, 


FIG.  12. — SECTION  OF  LIVER  UNDER  HIGH  POWER  OF  A  CASE  OF  ACUTE  YELLOW  ATRO- 
PHY, SHOWING  FATTY  DEGENERATION  OF  NECROSIS  OF  LIVER  CELLS.  Evidences 
of  reparative  process  are  seen  in  the  replacement  fibrosis.  A  few  islands  of  darkly 
staining  intact  cells  remain  (Ewing). 

characterized  clinically  by  the  well-known  picture  of  acute  yellow 
atrophy  and  frequently  complicating  a  hyperemesis. 

3.  Eclampsia,  characterized  by  focal  cell  degeneration  and 
necrosis,  as  the  result  of  thrombosis  of  the  smallest  vessels,  is 
represented  clinically  by  eclampsia  with  or  without  convulsions. 
Here  we  may  add,  there  is  no  change  in  the  size  of  the  liver  and 
subcapsular  hemorrhages  are  common. 


PATHOLOGY 


69 


Schwangerschaftsleber. — The  renal  changes  noted  are  not  the 
only  ones  associated  with  pregnancy.  As  in  the  kidney,  so  we 
find  minor  alterations  in  the  liver  resulting  from  gestation,  con- 
sisting of  a  mild  degree  of  fatty  infiltration  and  an  alteration  of 
function,  a  condition  the  Germans  have  called  Schwangerschaftsleber, 
or  pregnancy  liver,  which  may  by  gradual  transition  lead  to  acute 


FIG.  13. — SECTION  OF  A  KIDNEY  FROM  A  CASE  OF  ACUTE  YELLOW  ATROPHY  OF  THE 
LIVER,  SHOWING  EXTENSIVE  FATTY  DEGENERATION  OF  THE  LINING  CELLS  OF  THE 
TUBULES  (Ewing). 

yellow  atrophy  or  to  eclampsia.  The  milder  degrees  of  jaundice, 
"toxic  icterus,"  often  met  with,  are  probably  due  to  this  patho- 
logic condition.  The  resistance  of  the  individual  organs  in  any 
given  case  probably  determines  the  effect  of  the  toxin. 

NEPHRITIC  AND  PRE-ECLAMPTIC  TOXEMIAS 

Pathology. — The  pathology   of  these   two   toxemias   may  be 
considered  with  the  pathology  of  eclampsia.     The  presence  of  an 


70  TOXEMIAS  OF  PREGNANCY 

albuminuria  is  so  frequent  in  pregnancy  that  alterations  in  the 
kidney  structure  and  its  function,  as  well  as  that  of  the  liver  may 
be  assumed  to  exist.  When,  however,  mere  traces  of  albumin 
become  increased  to  i  per  cent,  or  more,  and  are  associated  with 
casts,  particularly  of  the  granular  variety,  a  true  kidney  involve- 
ment may  be  suspected.  In  many  of  these  cases  exacerbations  of 
an  earlier  nephritis  may  be  at  fault,  and  the  differentiation  may 
be  difficult  between  an  old  and  a  new  process.  In  the  pregnancy 
kidney,  however,  the  degenerative  processes  probably  predom- 
inate, whereas  in  nephritis  the  inflammatory  lesions  are  more 
prominent.  In  the  former,  the  lesion  involves  the  tubules  and 
epithelium,  leaving  the  glomeruli  more  or  less  free,  and  conse- 
quently a  return  to  normal  function  occurs  soon  after  labor. 

Functional  Renal  Tests. — The  histologic  study  of  the  kidneys 
in  these  types  of  pregnancy  kidneys  is  scarcely  satisfactory, 
because  of  the  transitions  found  between  various  forms  and  the 
numerous  gradations  from  one  type  to  another.  Functional  kid- 
ney tests  have  been  introduced  to  clear  up  the  pathological  physi- 
ology and  it  has  been  found  that  normal  kidneys  in  pregnant 
women  excrete  water,  sodium  chlorid  and  nitrogen  equally  as  well 
as  in  the  nonpregnant.  In  the  presence  of  renal  disturbances 
associated  with  pregnancy,  the  excretion  of  water  and  chlorids  is 
diminished,  although  the  nitrogen  is  unchanged.  This  insuffi- 
ciency often  goes  hand  in  hand  with  the  percentage  of  albumin, 
although  not  invariably.  Care  must  be  taken  in  interpreting  the 
pathology  of  the  kidneys  by  these  tests,  but  in  many  instances 
the  results  are  of  value  in  determining  a  pre-eclamptic  toxemia 
before  edema  or  other  signs  appear. 

ECLAMPSIA 

Renal  Lesions. — The  pathologic  studies  of  this  most  serious 
complication  of  pregnancy  have  not  been  productive  of  any  final 
opinion  which  might  definitely  establish  the  etiology  of  the  con- 
dition. 

Since  the  constant  association  between  albuminuria  and 
eclampsia  was  first  brought  to  the  attention  of  the  profession  by 
Lever  in  1843  the  importance  of  kidney  lesions  has  always  been 
dwelt  upon.  In  fact,  the  convulsions  and  the  coma  associated 
with  eclampsia  correspond  so  closely  to  the  convulsions  of 


PATHOLOGY  71 

nephritis  that  for  a  long  time  they  were  supposed  to  be  one  and 
the  same  thing.  More  thorough  histological  studies  have  shown, 
however,  that  the  kidneys  of  eclampsia  present  an  entirely  differ- 
ent anatomical  picture.  A  chronic  interstitial  inflammation  with 
constriction,  obliteration  of  the  cortex  and  the  vessels,  diminution 
in  size  and  sclerosis  are  the  predominant  characters  of  the  kidney 


FIG.  14. — SECTION  OF  KIDNEY  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  ACUTE  PARENCHY- 
MATOUS  LESIONS — HIGH  POWER  (Hull). 

of  nephritis.  In  eclampsia,  on  the  other  hand,  the  kidney  is  not 
diminished  in  size,  the  appearance  is  anemic,  the  cortex  cloudy 
and  in  many  instances  presents  small  punctate  ecchymoses.  The 
capsule,  as  a  rule,  is  not  adherent.  A  microscopic  examination 
shows  degenerative  changes  in  the  epithelium  and  vessels.  The 
epithelium  of  the  damaged  Urinary  tubules  is  apt  to  be  disin- 
tegrated, swollen  and  deprived  of  nuclei.  The  capillary  vessels 
are  filled  with  red  cells  showing  a  marked  vascular  stasis  and  may 
also  contain  actual  thrombi.  The  interstitial  tissues  of  the  kidney 


72  TOXEMIAS   OF   PREGNANCY 

seem  to  be  little  changed  and  the  process  involves  almost  entirely 
the  parenchyma  of  the  organs.  Infarcts  may  be  present  and  are 
due  to  the  migration  of  emboli  from  other  organs. 

In  a  collection  of  368  autopsies  after  eclampsia  made  by  Prutz, 
involvement  of  the  kidneys  was  stated  to  be  present  in  all  but 
seven,  and  these  findings  were  confirmed  by  Pollak  of  Vienna, 


FIG.  15. — SECTION  OF  KIDNEY  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  TUBULES  FILLED 
WITH  HYALINE  AND  GRANULAR  DETRITUS.  The  lining  cells  in  places  have  almost 
entirely  disappeared  (Hull). 

who   noted   renal   changes   in   98   per   cent   of    139   autopsies   of 
eclampsia  cases. 

Hepatic  Lesions. — So  much  attention  was  given  to  the  study 
of  renal  pathology  in  eclampsia  that  lesions  in  other  organs  were 
strangely  overlooked.  Although  Virchow  and  Scanzoni  both 
referred  to  the  frequency  of  liver  involvement,  the  characteristic 
pathological  changes  in  the  liver  of  eclampsia  cases  were  first 
definitely  made  known  by  the  observations  of  Pilliet  and  Letienne 


PATHOLOGY  73 

and  by  Schmorl.  The  liver  in  gross  appearance  presents  irregular 
hemorrhagic  areas  sometimes  of  large  extent.  On  section  there 
are  patches  of  alternating  light  and  dark  areas  which  give  a 
mottled  appearance  to  the  organ.  Section  shows  a  necrosis  in  the 
lobules  and  portal  spaces,  which  has  been  attributed  to  thrombosis 
in  the  small  portal  vessels  with  consequent  degeneration  (Fig.  18). 
In  Schmorl's  series  of  cases  this  condition  was  invariably 


FIG.  16. — LIVER  FROM  AN  ECLAMPTIC  (SAME  CASE  AS  FIG.  20),  SHOWING  EXTENSIVE 
DIFFUSE  SUBCAPSULAR  HEMORRHAGE.  Also  numerous  scattered  hemorrhages 
in  the  substance  with  cloudy  swelling  of  the  parenchyma.  There  was  no  cirrhosis 
or  arteriosclerosis  present. 

present;  and  according  to  this  author,  the  change  is  neither 
inflammatory  nor  a  fatty  degeneration,  but,  as  he  says,  an  anemia 
or  hemorrhagic  necrosis  which  is  especially  well  marked  in  the 
region  of  the  suspensory  ligament.  Closer  microscopic  study 
seems  to  demonstrate  the  origin  of  the  process  in  the  periportal 
connective  tissue,  so  that  the  periphery  rather  than  the  center  of 
the  acini  is  involved. 


74  TOXEMIAS  OF  PREGNANCY 

HISTOLOGY. — Konstantinowitsch,  in  describing  the  histology  of  the 
process,  states  that  the  earliest  change  in  the  liver  of  eclampsia  is 
an  alteration  in  the  liver  cells  and  the  endothelium  of  the  capil- 
laries in  the  peripheral  portion  of  the  lobules.  This  alteration 
increases  with  the  progress  of  the  disease,  until  the  liver  cells 
present  a  reticulated,  vacuolar  appearance.  At  the  same  time 
dilatation  and  congestion  of  the  capillaries  on  the  peripheral  por- 
tion of  the  lobules  appears,  which  are  due  to  an  impeded  circula- 
tion from  primary  thrombosis  of  the  vessels  in  this  part.  A 
necrosis  of  the  hepatic  cells  results. 


FIG.  17. — LIVER  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  EXTENDED  DISTRIBUTION  OF 
SUBCAPSULAR  HEMORRHAGES  (case  from  the  N.  Y.  Lying-in  Hospital). 

There  is  apparently  no  relation  between  the  extent  of  the 
necrotic  process  and  the  severity  of  the  convulsive  seizures,  for 
Schmorl  reports  one  case  with  twenty-six  convulsions  in  twenty- 
four  hours,  in  which  the  necrotic  areas  were  few  and  widely 
scattered,  while  in  another  case  where  death  took  place  forty 
minutes  after  the  only  convulsion,  about  one  half  of  the  liver 
parenchyma  was  necrotic.  Three  other  cases  are  reported  in 
which  similar  changes  were  present  without  any  convulsions,  and 
such  findings  may  account  for  fatalities  where  no  evidence  of  dis- 
ease was  previously  noted. 


PATHOLOGY 


75 


Another  important  contribution  to  the  subject  is  a  report  by 
Welch  of  the  autopsy  findings  in  12  cases.  Welch  divides  the 
liver  lesions  found  into  four  classes.  The  first  includes  hemor- 
rhagic  changes  in  and  about  the  portal  spaces.  This  condition  was 
found  in  6  cases,  2  of  which  had  no  convulsions.  The  second  class 


FIG.  1 8. — CROSS-SECTION  OF  LIVER  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  PERIPORTAL 

NECROSIS  AT  N  (Williams). 

includes  3  cases  which  showed  necrosis  in  the  center  of  the  liver 
lobule.  These  cases  were  diagnosed  clinically  as  eclampsia.  The 
third  class  includes  only  i  case,  in  which  there  was  no  hemorrhage 
but  a  general  swelling  of  the  cells,  with  autolysis.  The  fourth 
class  includes  2  cases  in  which  the  liver  alteration  was  a  very 
slight,  cloudy  swelling  of  the  parenchyma  with  no  hemorrhage  or 
necrosis.  The  kidneys  in  the  last  class  show  extensive  disintegra- 


76 


TOXEMIAS   OF   PREGNANCY 


tion  of  the  epithelium  to  about  the  same  degree  as  was  found  in 
the  kidneys  of  the  other  three  classes. 

The  kidney  lesions  were  similar  in  all  the  cases.  In  none 
was  the  lesion  a  uniform  one.  The  parenchyma  was  affected 
throughout,  but  in  some  parts  of  a  given  kidney  more  destruction 
was  present  than  in  other  parts  of  the  same  organ.  Welch 


FIG.  19. — SECTION  OF  LIVER  FROM  A  CASE  OF  ECLAMPSIA  UNDER  HIGH  POWER.  Shows 
thrombosis  and  necrosis  of  the  hepatic  arterioles,  with  infarcts  of  the  surrounding 
liver  cells  (Ewing). 

believes  that  the  hemorrhages  and  necroses  are  not  due  to 
thrombi  resulting  from  hyaline  blood  plates  or  from  giant  cell 
emboli  in  the  liver  parenchyma,  as  explained  by  the  earlier 
investigators.  Although  all  of  these  have  been  found  in  certain 
instances,  it  would  be  difficult  to  imagine  that  the  extensive 
hemorrhages  so  commonly  found  throughout  the  body  in  eclamp- 
sia are  due  to  multiple  emboli. 

Welch    found    that    most    of   his    cases    showed    considerable 


PATHOLOGY 


77 


hemolysis.  The  masses  described  as  fibrin  in  the  hemorrhages 
of  the  liver  do  not  appear  as  clear-cut  fibrin  fibrils,  but  have  a 
hyaline  appearance  which  in  places  appeared  like  fused  red  blood- 


FIG.  20. — SECTION  OF  A  LIVER  FROM  A  CASE  OF  ECLAMPSIA.  Shows  the  process  of 
thrombosis  of  the  periportal  vessels  and  necrosis  of  the  liver  cells  at  the  periphery 
of  the  lobule  (Ewing). 

cell  stroma.  There  were  also  found  within  the  vessels  agglutin- 
ated red  cells  fused  into  hyaline  appearing  masses.  As  it  has  been 
shown  by  experiment  that  hemolysis  from  the  action  of  poisons 
is  first  preceded  by  agglutination  and  fusion  of  the  red  cells  before 


78  TOXEMIAS   OF   PREGNANCY 

they  undergo  solution  and  give  up  their  hemoglobin,  Welch 
believes  it  is  possible  that  the  condition  found  in  the  parenchyma 
cells  indicates  the  action  of  some  dissolving  poison.  He  asserts 
that  the  latter  can  also  attack  the  endothelium  of  the  blood  ves- 
sels and  that  the  hemorrhages  may  be  explained  through  these 
agencies.  The  reason  that  the  hemorrhages  are  more  numerous 
in  the  liver  is  because  the  toxin  in  the  blood  is  reenforced  by  that 
of  the  liver.  If  to  these  causes  we  add  the  increased  blood-pres- 
sure which  is  usually  found,  the  large  brain  hemorrhages  may  be 
accounted  for,  for  these  occur  in  young  subjects  who  are  usually 
free  from  arteriosclerosis.  Welch  claims  that  the  poison  which 
causes  such  serious  intoxication  is  probably  an  enzyme  or  a  com- 
bination of  enzymes.  If  these  enzymes  are  distributed  in  some 
hitherto  unknown  manner  they  will  attack  the  cells  in  which  they 
reside  and  cause  their  destruction,  or,  in  other  words,  the  process 
known  as  autolysis  will  take  place.  As  the  liver  cells  are 
especially  rich  in  these  enzymes,  the  greatest  destruction  occurs 
at  this  point. 

Hemorrhages. — Although  kidneys  and  liver  present  the  most 
frequent  and  most  characteristic  pathologic  changes  at  autopsy, 
almost  all  the  organs  may  be  more  or  less  involved.  Hemor- 
rhages may  take  place  into  the  lungs  and  pleura,  pericardium, 
cranial  cavity  and  brain,  gastric  mucosa,  peritoneum  and  skin. 
Welch  in  his  series  reports  a  cloudy  swelling  of  all  the  involved 
organs,  most  easily  seen  in  the  heart  muscle  and  other  unstriped 
muscles  throughout  the  body.  Marked  hemolysis  is  to  be  ob- 
served in  these  cases,  and  there  is  usually  more  or  less  effused 
blood  in  the  body  cavities,  colored  by  the  blood  pigment  liberated 
by  the  process. 

Pulmonary  thrombosis  has  frequently  been  observed,  marked 
by  the  finding  of  "giant  cells"  in  the  capillaries,  which  are  sup- 
posedly of  placental  origin.  The  fact  that  such  emboli  are  found 
in  pregnant  women  dying  of  other  diseases  contradicts  the  claim 
that  they  are  the  cause  of  the  thrombotic  processes.  Fat  emboli 
also  occur  in  the  lungs  but  are  probably  not  of  pathological  origin, 
being  derived  from  the  normal  fat  deposits  in  the  subcutaneous 
or  connective  tissues  and  the  bone  marrow.  They  probably  result 
from  the  convulsions.  Bronchopneumonia  and  an  extensive  pul- 
monary edema  are  often  found  in  cases  progressing  to  a  fatal 
ending  several  days  after  convulsions  have  ceased.  There  is 


PATHOLOGY 


79 


nothing  characteristic  in  such  lesions,  nor  in  the  development  of 
septicemic  foci  sometimes  found. 

Hemorrhagic  lesions  in  the  brain  have  been  noted  in  most 
autopsies  in  eclamptic  subjects,  both  substance  and  cortex  being 
involved  (Figs.  21,  22).  In  addition  diffused  areas  of  cortical 
softening  are  frequently  observed  as  well  as  edema  or  hyperemia,  al- 


FlG.  21. — VIEW  OF  THE  BRAIN  L.\ID  OPEN,  FROM  A  CASE  OF  PoST-PARTUM  ECLAMPSIA 

IN  A  PRIMIPARA  IN  ECLAMPSIA  WITH  A  SINGLE  CONVULSION.  The  ventricles  were 
distended  with  blood  and  many  petechial  hemorrhages  were  scattered  over  the 
surface.  In  the  lower  part  of  the  pons  a  hemorrhage  ruptured  into  the  fourth 
ventricle.  The  vessel  walls  in  this  specimen  all  showed  a  cloudy  swelling  indicat- 
ing the  probable  acute  action  of  a  circulating  toxic  substance.  The  liver  from 
this  case  is  shown  in  Fig.  16  (N.  Y.  Lying-in  Hospital  case). 

though  edema  is  probably  not  reported  as  often  as  it  occurs,  because  of 
its  rapid  subsidence  after  death.  The  hemorrhages  are  probably 
thrombotic  in  most  instances  but,  as  Welch  has  pointed  out,  the 
vess'els  may  rupture  as  the  result  of  the  solvent  action  on  the 


8o 


TOXEMIAS  OF   PREGNANCY 


endothelial  lining-  by  a  circulating  toxic  enzyme  aided  by  the 
increased  blood-pressure.  The  extent  of  the  bleeding  varies  from 
that  of  small  degree  in  the  pons,  as  shown  in  Fig.  20,  to  an 
extensive  effusion  into  the  lateral  ventricals  (Fig.  21),  which 
distends  their  cavities  and  lacerates  the  walls.  True  cerebral 
apoplexies  are  also  found,  usually  in  the  distribution  of  the  middle 
temporal  artery ;  and  in  those  cases  of  eclampsia  where  hemi- 


FIG.  22. — BRAIN  LAID  OPEN,  FROM  A  CASE  OF  ECLAMPSIA  WITH  CONVULSIONS.  Shows 
extensive  traumatic  hemorrhage  into  the  fourth  ventricle  (case  from  the  N.  Y. 
Lying-in  Hospital). 

plegia  or  other  paralytic  lesions  develop,  cortical  hemorrhages  in 
the  motor  areas  have  probably  occurred,  with  or  without  recov- 
ery. The  high  blood-pressure  associated  with  the  disease  pre- 
disposes to  the  occurrence  of  these  hemorrhages,  but  since  vene- 
section has  been  revived  a  reduction  in  the  incidence  of  this  lesion 
has  been  observed. 

Cerebral  Edema. — Edema  of  the  brain,  with  its  resultant  intra- 
cranial  pressure,  is  declared  by  Zangemeister  to  be  the  cause  of 


PATHOLOGY  81 

eclampsia.  He  diagnosed  this  edema  as  an  actual  "glaucoma  of 
the  brain,"  and,  in  three  severe  cases,  attempted  to  relieve  the 
tension  by  prompt  osteoplastic  resection  of  the  skull.  After  turn- 
ing back  a  bone  flap  on  the  right  side  above  and  behind  the 
temple,  the  dura  was  found  hard  and  tense,  the  pressure  being  so 
great  that  there  was  no  pulsation.  Large  quantities  of  serous 
fluid  escaped  after  incising  the  dura  and  the  convulsions  subsided. 
Two  of  the  three  patients  recovered.  One  of  the  cases  in  which 
the  dura  was  sutured  died  on  the  sixth  day,  and  Zangemeister 
believed  that  the  edema  probably  recurred. 

Hemorrhage  of  Heart  and  Other  Organs. — The  heart  in  fatal 
eclampsias  shows,  on  examination,  hemorrhages  into  its  sub- 
stance, together  with  areas  of  necrosis  and  albuminoid  degenera- 
tion of  the  muscle  fibers.  Hemorrhagic  and  necrotic  areas  are 
less  frequent  in  the  pancreas  and  suprarenal  bodies. 

Traumatic  Lesions. — The  serious  character  of  traumata  to 
internal  organs  that  may  take  place  in  eclampsia  is  well  shown 
in  the  report  of  a  case  by  Lobenstine  and  Welch.  The  patient,  a 
primipara,  developed  severe  convulsions  about  eight  hours 
after  delivery  which  were  succeeded  by  a  condition  of  coma  with  a 
fatal  issue  twenty-four  hours  later.  The  autopsy  showed  in  addi- 
tion to  the  usual  lesions  in  the  internal  organs,  an  extensive 
rupture  of  the  diaphragm  and  several  perforations  of  the  posterior 
wall  of  the  stomach.  The  mucous  membrane  of  the  latter  was 
markedly  congested  and  contained  many  small  hemorrhages. 
These  ruptures  probably  occurred  during  the  period  of  convul- 
sions, although  the  patient  apparently  survived  them  several 
hours.  Traumatism  from  treatment  could  be  excluded  in  this 
case. 

That  pregnancy  toxemias  predispose  to  uterine  hemorrhages 
among  other  complications,  has  been  shown  in  several  investiga- 
tions. Thus,  Davis-Colby  demonstrated  in  a  series  of  cases  that 
such  bleeding  often  constitutes  the  chief  symptom.  He  proposed 
the  following  classification  for  hemorrhages  associated  with 
toxemia:  (i)  Hemorrhage  from  the  kidney.  Of  36  cases  with 
eclampsia,  hematuria  was  present  in  10,  of  which  6  died.  (2) 
Hemorrhage  from  the  uterus.  In  13  cases  of  accidental  hemor- 
rhage there  were  8  which  showed  unmistakable  evidences  of  tox- 
emia; whereas  where  external  bleeding  took  place,  as  from 
placenta  praevia,  there  was  only  one  instance  of  toxemia  in  30 


82  TOXEMIAS  OF  PREGNANCY 

cases.  (3)  Purpura  and  bleeding  from  the  mucous  membranes, 
in  which  the  prognosis  must  be  regarded  as  unfavorable. 

Smyly  also  inclines  to  the  opinion  that  most  cases  of  severe, 
and  especially  of  concealed,  internal  hemorrhage  are  due  to 
toxemia  and  will  usually  be  found  associated  with  albuminuria 
and  other  symptoms  of  this  condition.  Smyly  also  calls  attention 
to  the  fact  that  when  cesarean  section  is  performed  in  these  cases, 
the  blood  will  be  found  not  only  in  the  uterine  cavity  but  also  in 
its  wall,  separating  and  injuring  the  muscle  cells.  Hemorrhage 
into  the  pelvic  cellular  tissue  between  the  folds  of  the  broad  liga- 
ment and  in  the  peritoneal  cavity  itself  has  also  been  noted  in  such 
cases.  When  premature  separation  of  the  placenta  occurs,  edema 
of  the  uterine  walls  is  frequently  observed  and  in  a  series  of  8 
cases  reported  by  the  author  at  a  meeting  of  the  Royal  Society  of 
Medicine  in  1916,  albuminuria  was  present  in  every  instance.  In 
5  of  this  series,  moreover,  a  large  hematoma  in  the  broad  ligament 
was  found,  and  in  2  others,  there  was  free  blood  in  the  peritoneal 
cavity.  In  these  cases  not  only  was  the  placenta  more  or  less 
detached  and  the  uterine  cavity  filled  with  blood,  but  blood  was 
also  extravasated  into  the  uterine  walls,  especially  under  the  peri- 
toneal coat. 

Ocular  Lesions. — The  frequency  of  visual  disturbances  should 
have  inspired  numerous  studies  in  the  pathology  of  the  eye  in 
eclampsia,  but  few  references  are  available.  In  addition  to  more 
or  less  diffused  retinal  hemorrhages,  actual  rupture  of  the  retina 
may  occur,  as  shown  in  a  report  by  Schiotz,  who  presents  the 
records  of  three  cases  of  retinal  detachment  during  pregnancy 
with  nephritis.  The  patients  were  primiparae,  seventeen,  twenty- 
nine,  and  thirty-five  years  of  age  respectively,  with  albuminuria 
and  convulsions,  but  without  pronounced  edema.  The  detachment 
occurred  after  several  convulsions.  In  the  oldest  case  at  the 
seventh  month  of  pregnancy  it  was  bilateral,  and  persisted  for  a 
month  after  labor,  when  a  return  to  the  normal  resulted.  In  a 
subsequent  pregnancy  five  years  later,  no  visual  disturbances 
were  noted.  In  the.  twenty-nine-year-old  patient  there  was  also 
retinitis  and  detachment  which  persisted  for  two  weeks  until 
delivery  at  the  seventh  month,  when  the  retina  returned  to  place. 
The  youngest  patient  developed  convulsions  after  delivery  at 
term  and  the  detachment  occurred  without  any  retinitis  and  per- 
sisted. 


PATHOLOGY  83 

Placental  Infarcts. — The  theory  that  eclampsia  is  caused  by  a 
placental  poison  has  directed  attention  to  the  anatomical  study 
of  this  organ,  in  which  infarcts  and  hemorrhages  have  been  so 
frequently  observed.  Placental  infarcts  are  said  to  stand  in  a 
direct  relation  to  albuminuria  and  toxemia  by  a  number  of  investi- 
gators (Holland  for  one),  although  whether  as  a  cause  or  a  con- 
sequence does  riot  appear  to  be  definitely  settled.  The  condition 
may  undoubtedly  exist  without  any  evidences  of  toxemia  and  the 
contrary  also  holds  good.  Williams  found  in  his  series  of  cases 
that  infarct  formation  is  not  particularly  marked  in  acute  cases  of 
eclampsia,  but  is  usually  observed  where  marked  albuminuric 
symptoms  are  present.  Young,  who  has  contributed  a  classical 
study  on  this  subject,  believes  that  in  acute  toxemia  ending 
rapidly  in  labor,  the  placenta  may  present  evidences  of  disease 
or  look  perfectly  normal  to  the  naked  eye.  If,  on  the  other  hand, 
the  acute  attack  passes  off  and  labor  supervenes  ten  to  fourteen 
days  later,  extensive  recent  necrosis  will  be  found.  Young  regards 
this  fact  as  sufficient  evidence  of  the  causative  role  of  autolytic 
changes  in  the  affected  organ.  He  proceeds  to  demonstrate  this 
by  anatomical  data  and  experimental  results.  I  consider  the 
matter  of  importance  enough  from  the  pathologic  standpoint  to 
warrant  a  somewhat  detailed  presentation  of  his  view  because  of 
its  bearing  on  the  etiology  of  eclampsia. 

ORIGIN. — In  attempting  an  explanation  of  the  cause  of  placental 
infarction,  Young  directs  attention  to  the  very  loose  connection 
between  the  fully  developed  placenta  and  the  uterine  wall — a  thin 
decidual  film  being  all  that  binds  the  two  together.  This  film 
bridges  across  the  large  venous  channels,  so  that  the  placenta 
seems  to  rest  on  a  greatly  expanded  blood  lake.  Where  the  ves- 
sels perforate  the  placenta  the  film  is  absent  and  there  are  other 
places  where  the  villi  dip  deeply  into  the  blood  spaces.  Veit 
believed  that  deportation  of  the  villi  occurred  through  these  open- 
ings into  the  blood  stream.  Although  this  anatomical  arrange- 
ment provides  for  ease  of  separation,  it  also  affords  an  oppor- 
tunity for  vascular  disturbance  including  the  formation  of  pla- 
cental infarcts.  It  may  be  remarked  in  passing  that  there  are  two 
theories  regarding  the  origin  of  the  latter: 

i.  Eden,  Williams  and  others  believe  that  placental  infarct  is 
due  to  a  change  commencing  primarily  in  the  villi  themselves. 
The  blood  supply  is  interfered  with  as  the  result  of  an  obliterating 


84  TOXEMIAS   OF   PREGNANCY 

change  in  the  vessels,  which  leads  to  a  degeneration  of  the  epi- 
thelium and  stroma  of  the  villi,  and,  secondarily,  to  a  coagulation 
of  the  maternal  hlood. 

2.  According  to  another  theory  the  degeneration  is  due  to  an 
interference  with  the  maternal  blood  supply.  Let  us  quote  Young 
directly  in  discussing  these  theories: 

"The  first,  the  most  commonly  accepted  idea  naturally 
assumed  that  the  villi  are  dependent  for  their  nourishment  upon 
the  fetal  blood  supply,  and  that  once  this  is  obstructed  they  must 
undergo  progressive  necrosis.  If  one  could  show  definitely  that 
the  villous  structures  are  independent  of  the  fetal  blood,  and, 
moreover,  can  live  and  proliferate  when  this  is  removed,  so  long 
as  the  maternal  supply  remains  intact,  it  would  render  this 
explanation  of  the  infarction  process  untenable.  This  is  not  dif- 
ficult to  do.  There  are  several  considerations  which  show  it: 

"(0  The  time  when  the  chorionic  elements  are  most  active 
and  proliferate  most  rapidly  is  during  the  early  stages  of  the 
development  of  the  ovum,  where  there  are,  as  yet,  no  fetal  vessels 
formed,  and  where  the  trophoblast  and  its  villi  obviously  live 
directly  upon  the  mother's  blood. 

"(2)  In  hydatid  mole  the  chorionic  villi  live,  and,  as  we  know, 
actively  proliferate,  when  there  is  not  a  trace  of  a  fetal  vessel,  and 
when  the  entire  nourishment  is  derived  from  the  blood  of  the 
mother.  The  same  is  true  of  chorionepithelioma. 

"(3)  In  tubal  pregnancy  one  can  sometimes  recognize  the 
independence  of  the  villi  of  the  fetal  blood  in  a  diagrammatic 
manner.  Where  there  has  been  a  considerable  hemorrhage  into 
the  extrachorionic  space  great  masses  of  villi  become  strangled 
in  blood-clot.  I  have  seen  one  such  case  where  all  the  trunks  in 
the  neighborhood  of  the  chorion  had  undergone  fibrinous  necro- 
sis, but  near  the  tube  wall,  where,  in  parts,  the  maternal  circula- 
tion was  unimpaired,  the  tips  of  the  necrotic  villi  remained 
healthy. 

''These  facts  demonstrate  beyond  doubt  that  the  villi,  even 
after  the  fetal  blood  supply  is  removed,  can  live,  so  long  as  the 
maternal  supply  remains  uninvolved." 

It  is  evident,  if  this  reasoning  is  correct,  that  localized  patches 
of  dead  placental  tissue  result  from  an  interference  with  the 


PATHOLOGY  85 

maternal  blood  supply;  for,  as  Young  pointed  out  elsewhere,  in 
by  far  the  largest  number  of  cases,  infarcted  areas  lie  in  close 
relation  to  the  decidual  surface,  and  in  such  cases  degeneration, 
often  necrosis,  of  the  decidua  may  be  detected.  Furthermore, 
small  nodules  of  healthy  placenta  may  sometimes  be  seen  on  the 
decidual  aspect  of  large  infarcts,  which  means,  according  to 
Young,  that  whereas  the  remainder  of  the  infarcted  portion  has 
lost  its  nourishment,  the  healthy  nodule  has  retained  its  maternal 
supply.  This,  however,  is  admitted  to  be  a  rare  occurrence. 

Young  believes  that  another  convincing  proof  of  the  maternal 
origin  of  infarcts  lies  in  the  changes  associated  with  placental 
hemorrhage,  for  where  retroplacental  hemorrhage  has  resulted, 
the  adjoining  placenta  is  diseased,  provided  a  certain  time  has 
elapsed. 

Young  contends  that  the  interference  of  the  blood  supply 
which  is  responsible  for  the  infarction  is  not  dependent  upon  a 
toxic  state,  and,  in  point  of  fact,  may  occur  in  the  most  extreme 
form  where  there  is  no  evidence  of  a  toxemia,  as  for  example,  in  acci-5 
dental  hemorrhage.  Furthermore,  the  placenta  is  so  constructed 
that  if  a  part  of  it  dies,  the  products  liberated  from  the  dying 
patch  can  pass  directly  into  the  blood  stream.  It  is  apparently 
necessary,  therefore,  from  the  anatomic  standpoint,  that,  for  the 
occurrence  of  a  toxemia,  the  blood  must  circulate  around  the 
poison-generating  foci.  Young  believes  that  an  understanding 
of  this  fact  at  once  dispels  many  of  the  difficulties  associated  with 
the  study  of  this  condition.  It  explains,  for  example,  the  cessation 
of  symptoms  after  the  death  of  the  child  and  the  separation  of  the 
placenta  and  also  explains  the  absence  of  a  toxemia  in  cases  of 
accidental  hemorrhage  in  which  the  placenta  is  completely  de- 
tached by  the  blood-clot.  The  cases  of  accidental  hemorrhage 
associated  with  toxemia  are  those  in  which  part  of  the  placenta 
remains  attached  for  some  time  after  the  separation  of  the  adja- 
cent portion  by  the  retroplacental  bleeding.  It  is  the  necrosis  of 
this  part  which  liberates  the  toxic  materials.  These  facts,  accord- 
ing to  Young,  suggest  that  the  toxemias  are  due  to  the  autolytic 
products  liberated  in  the  early  stages  of  placental  death  (see 
Figs.  6,  7,  8,  9).  He  attempted  to  imitate  this  process,  which 
occurs  in  utcro,  by  isolating  from  the  healthy  placenta  the  soluble  sub- 
stances which  reproduce  the  clinical  features  and  morbid  changes 
characteristic  of  eclampsia,  including  convulsions,  peripheral  focal 


86  TOXEMIAS   OF   PREGNANCY 

necrosis  in  the  liver  and  degenerative  lesions  in  the  convoluted 
tubules  of  the  kidney.  The  occurrence  of  post-partum  eclampsia  is  in 
apparent  opposition  to  this  theory,  but  Young  believes  that  even  small 
pieces  of  retained  placenta  may  act  in  the  manner  described  above. 

Experimental  reproduction  of  eclampsia  was  carried  out  in  guinea 
pigs.  Carefully  prepared  dry,  powdered  placenta  and  glycerin 
extracts  of  placenta  were  administered  subcutaneously  in  varying 
doses  to  47  animals.  Severe  and  prolonged  muscular  spasms  devel- 
oped within  less  than  a  minute,  accurately  reproducing  an  eclamptic 
seizure.  The  placental  powder  seemed  to  be  the  most  effective 
in  producing  symptoms  and  death  usually  occurred  in  these  cases. 
Autopsies  showed  typical  degenerative  lesions  in  the  liver  with 
similar  but  less  marked  examples  in*  the  kidneys.  The  glycerin 
extracts  seemed  to  produce  even  more  marked  necrotic  changes, 
although  the  convulsive  symptoms  were  absent,  or  less  marked. 
This  condition  seems  to  correspond  with  the  clinical  differences 
observed  in  eclampsia  in  the  human  subject  where  convulsions  are 
the  chief  symptom  in  one  group,  whereas  they  may  be  absent  in 
the  other,  although  in  each  case  the  resulting  pathological  lesions 
seem  to  be  the  same.  Further  investigation  in  the  directions 
referred  to  in  Young's  article  may  lead  to  a  more  satisfactory 
knowledge  regarding  certain  fields  of  investigation  in  eclampsia 
which  have  hitherto  been  apparently  neglected. 

Differential  Diagnosis. — The  differential  diagnosis  Setween 
eclampsia  and  other  conditions  characterized  by  convulsive 
seizures  is  often  only  made  at  autopsy.  Thus  Croom  reports  2 
cases  which  closely  simulated  eclampsia  but  in  both  of  which  the 
urinary  changes  were  entirely  absent.  In  one  instance  there  was 
a  large  tumor  of  the  left  anterior  parietal  region,  fatty  and 
catarrhal  changes  in  the  kidneys,  and  fatty  degeneration  of  the 
liver  and  heart.  The  tumor  consisted  essentially  of  epithelium 
with  a  supporting  stroma  of  connective  tissue.  There  were  no 
symptoms  directly  referable  to  the  cerebral  neoplasm  and  death 
was  apparently  due  to  eclampsia.  In  the  second  case  a  similar 
train  of  symptoms  was  found  to  be  due  to  tubercular  meningitis. 

Conclusion. — Summing  up  the  autopsy  findings  of  eclampsia 
we  note  that  the  most  constant  lesions  are  hemorrhage,  princi- 
pally in  the  liver,  and  degenerative  processes  which  involve  any 
one  or  nearly  all  of  the  essential  internal  organs.  Their  distri- 
bution, extent  and  individual  characteristics  vary  widely  and  the 


PATHOLOGY  87 

paucity  in  certain  fatal  cases  with  few  clinical  symptoms  and  their 
frequency  in  others  would  make  it  appear  that  their  presence  is 
secondary  to  the  presence  in  the  circulation  of  some  toxic  sub- 
stance. The  nature  of  this  toxic  substance  is  still  unknown,  but 
it  seems  to  predispose  to  hemorrhage  through  its  possibly  solvent 
action  on  the  endothelial  lining  of  the  blood  vessels,  as  pointed  out 
by  several  observers.  That  this  toxic  material  may  possibly  be 
transmitted  to  the  fetus  seems  a  reasonable  supposition,  as  similar 
lesions  are  found  after  death  in  the  babies  of  eclamptic  mothers. 
These  babies  usually  die  in  convulsions,  within  the  first  few  days 
after  birth. 

LITERATURE 

BAR  ET  GUYEISSE.     Lesions  du  foie  et  des  reins  chez  les  eclamptiques 

et  les  foetus  issus  des  femmes  eclamptiques.     Obstetrique,  Par., 

1897,  2,  263. 

BEHM.    Arch.  f.  Gynak.,  Berl.,  1906,  69,  410. 
BONDY,  O.    Zur  Lehre  von  der  Hyperemesis  gravidarum.    Monatschr. 

f.  Geburtsh.  u.  Gynak.,  Berl.,  1914,  39,  751. 
BUSCHMANN,  T.  W.     Unilateral  Impairment  of  the  Kidney  in  the 

Toxemia  of  Pregnancy.    Am.  Journ.  Obst,  1915,  72,  624. 
CHIRIE,  C.  L.     Corpus  Luteum  und  unstillbares  Erbrechen.     Gynak. 

Rundsch.,  1912,  6,  No.  19). 

CROOM.    Journ.  Obst.  and  Gyn.  Brit.  Emp.,  1912,  April  23. 
DAVIS-COLBY.    Brit.  M.  J.,  1912,  Feb.  16. 
DUNCAN.    Lond.  Med.  Times  and  Gaz.,  1879,  I,  57. 
ERISMAN.    Dissert.,  Basel,  1890. 
EWING.    Amer.  Journ.  Obst,  1905,  71,  145. 
FELLANDER.     1st  die  Eklampsie  eine  anaphylaktische  Erscheinung? 

Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1911,  68,  26. 
FRANK  AND  HYMAN.     The  Placental  Theory  of  Eclampsia.     Surg., 

Gyn.  and  Obst.,  1911,  12,  451. 
GESSNER,   W.     Ueber  die   Leberveranderungen  bei  der  Eklampsie. 

Gynak.  Rundsch.,  1916,  10,  (Nos.  i  &  2). 
GRAFFENBURG.     Die  anaphylaktischen  Beziehungen  zwischen  Mutter 

und  Kind.    Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1911,  69,  207. 
GUGGISBERG.     Experimentelle  Untersuchungen  iiber  die  Toxikologie 

der  Placenta.     Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1910,  67, 

84. 


88  TOXEMIAS  OF   PREGNANCY 

HAEGLER.      Zur   Frage    "Eklampsiebacillus"    Gerdes.      Centralbl.    f. 

Gynak.,  Leipz.,  1892,  16,  996. 
HALBERTSMA.      Ueber    die    Aetiologie    der    Eklampsie    puerperalis. 

Samml.  klin.  Vortr.,  Gyn.  n.  F.,  Leipz.,  1884,  (No.  212). 
HEINRICHSDORF.    Arch.  f.  Gynak.,  Berl.,  1913,  99,  43. 
HEINRICHSDORF      Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1912,  70, 

620. 

HOLLAND.    Journ.  Obst.  and  Gyn.  Brit.  Emp.,  1909,  16,  255. 
INGERSLEV.      Beitrag    zur    Albuminuria    wahrend    Schvvangershaft, 

Geburt  und  Eklampsie.     Ztschr.  f.  Geburtsh.  u.  Gynak.,  Stuttg., 

1881,  6,  171. 
JARDINE  AND  KENNEDY.     Symmetrical  Necrosis  of  the  Cortex  of  the 

Kidney    associated    with   puerperal   Eclampsia.      Trans.    Edinb. 

Obst.  Soc.,  1912,  38,  158. 
KLEBS.     Multipel  Leberzellen  Thrombose.     Beitr.  z.  path.  Anat.  u.  z. 

allgm.  Path.,  Jena,  1888,  3,  30. 
KONSTANINOWITSCH.     Beitr.  z.  path.  Anat.  u.  z.  allgm.  Path.,  Jena, 

1907,  40,  483. 

LEVER.    Guy's  Hosp.  Rep.  Lond.  sec.  ser.,  1843,  J>  495- 
LINDEMANN.    Zur  pathologischen  Anatomic  des  unstillbaren  Erbrech- 

ens  der  Schwangeren.     Centralbl.  f.  allgm.  Path.  u.  path.  Anat., 

Jena,  1892,  3,  625. 

LOBENSTINE  AND  WELCH.    Bull.  Lying-in  Hosp.,  N.  Y.,  No.  2. 
OPEL.     Zonal  Necrosis  of  the  Liver.     Journ.  Med.  Research,  1904, 

12,  147. 
PEARCE  AND  JACKSON.    Experimental  Liver  Necrosis.     Studies  from 

the  Bender  Hyg.  Lab.,  1907,  4,  35. 

PICK.    Samml.  klin.  Vortr.,  Gyn.  n.  F.,  Leipz.  ,1902,  Nos.  325,  326. 
PILLIET  ET  LETIENNE.    Nouv.  arch,  d'obst.  et  de  gynec.,  1889,  4,  312. 
PRUTZ.     Ueber  das  anatomische  Verhalten  der  Nieren  bei  der  Puer- 

peraleklampsie.     Ztschr.   f.  Geburtsh.  u.  Gynak.,   Stuttg.,   1892, 

33.  i- 
QUINCKE.   Akute  Leberatrophie.   Nothnagel's  Spec.  Path.  u.  Therap., 

1899,  1 8,  294. 

SCHICKELE.    Arch.  f.  Gynak.    Berl.,  1909,  92,  417. 
SCHICKELE.,  G.    Ueber  die  sogennante  Schwangerschaftsleber  und  die 

Leberinsuffizienz.    Gynak.  Rundsch.,  1912,  6,  (No.  20). 
SCHIOTZ.     Quoted  in:  Journ.  A.  M.  A.,  1914. 
SCHMORL.     Path.  anat.  Untersuchungen  iiber  Puerperal-Eklampsie, 

Leipz.,  1893;  also  in  Arch.  f.  Gynak.,  Berl.,  1902,  65,  504. 


PATHOLOGY  89 

SEITZ.     In:    Doderlein's  Handb.  der  Gebzurtshilfe,  1916,  2,  220. 

SMYLY.     Lancet,  Lond.,  1919,  Jan.  25. 

STOXE.    Amer.  Gyn.,  1903,  3,  518. 

VEIT.     Die  Verschleppung  der  Chorionzotten.     Wiesbaden,  1905. 

WELCH.    Amer.  Journ.  Obst.,  1919,  59,  i. 

WERNER   AND   KOLISCH.      Vergleichende   Untersuchungen   iiber   die 

Giftigkeit  von  Harn,  Serum  und  Milch.     Arch.  f.  Gynak.,  Berl., 

1914,  103,  222. 

WILLIAMS.    Amer.  Journ.  Obst.,  1900,  41,  775. 
WILLIAMS.    Journ.  Obst.  and  Gyn.  Brit.  Emp.,  1912,  22,  245. 
WOLFF  UND  ZADE.    Zur  Diagnose  und  Prognose  der  Nierenverander- 

ungen   in   der    Schwangerschaft.      Monatschr.    f.    Geburtsh.    u. 

Gynak.,  Berl.,  1914,  40,  639. 

YOUNG.    Proc.  Roy.  Soc.  Med.  Lond.,  1914,  7,  307. 
ZIXSSER,  A.     Ueber  die  Schadigung  der  Niere  bei  der  Eklampsie. 

Berl.  klin.  Wchnschr.,  1913  (March  3,  No.  9). 


CHAPTER  IV 

TREATMENT 

Treatment  of  hyperemesis — Physical  examination — Correction  of  uterine  displace- 
ments and  stenoses — Cauterization  of  cervical  erosions — Diet — Corpus  lutein 
extract — Laxatives — Rest — Routine  care — Rectal — Emptying  the  uterus — Sup- 
plementary measures  —  Acute  yellow  atrophy  —  Nephritis  and  eclampsia  — 
Prophylactic  measures — Constipation — Care  of  organs  of  elimination — Blood- 
pressure  observations — Visual  disturbances — Treatment  of  convulsions — Induc- 
tion of  labor — Rectal  infusions — Post-partum  care — Urine  examinations — 
Summary  of  specific  plan  of  treatment — Conservative  and  radical  venesection 
— Skull  trephining  and  lumbar  puncture — Infusions  of  magnesium  sulphate — 
Ductless  gland  therapy — Necessity  for  carbohydrates — Intravenous  injections 
of  glucose — Literature. 

General. — In  any  endeavor  to  describe  the  treatment  of  the 
various  toxemias  of  pregnancy,  the  cardinal  fact  to  be  borne  in  mind  is, 
that  no  routine  method  applicable  to  any  or  all  classes  of  cases 
can  be  recommended,  but  that  in  each  instance,  particularly  in  the 
severer  types,  consideration  must  be  given  to  the  individual 
patient.  In  this  connection  I  am  reminded  of  a  comment  made  by 
the  late  Professor  Delafield  of  the  College  of  Physicians  and  Sur- 
geons in  New  York  when  lecturing  on  the  treatment  of  pneu- 
monia: "Always,"  he  cautioned  his  students,  "treat  the  patient 
and  not  the  disease."  This  warning  can  be  applied  equally  well 
to  the  subject  matter  in  hand  and  my  personal  experience  prompts 
me  to  preface  the  description  of  the  treatment  of  these  disorders 
by  the  insistence  that  each  case  of  toxemia  be  treated  individually 
and  that,  while  we  can  follow  certain  general  and  well-recognized 
routine  procedures  in  certain  groups  of  cases,  they  must  be 
changed  as  circumstances  may  dictate.  In  order  to  apply  such 
individual  treatment  the  underlying  etiological  factors  should  be 
determined,  if  possible,  so  that  an  intelligent  handling  of  the  case 
can  be  undertaken.  For  example,  in  the  vomiting  of  early  preg- 
nancy, the  possible  reflex  or  anatomical  causes  must  be  carefully 
sought  out  before  instituting  treatment,  because  if  they  are  pres- 
ent the  case  cannot  be  regarded  from  the  toxic  standpoint  alone, 

90 


TREATMENT  91 

but  must  be  treated  with  the  measures  which  have  been  recom- 
mended for  this  type  of  vomiting.  Nor  in  the  toxemias  associated 
with  the  latter  months  of  pregnancy,  is  every  woman  who  pre- 
sents a  headache,  or  pain  in  the  pit  of  the  stomach,  to  be  regarded 
as  a  possible  eclamptic,  nor  should  every  case  in  which  convulsive 
movements  occur  be  subjected  to  the  eliminatory  treatment 
proper  for  true  eclampsia.  The  differentiation  of  these,  conditions 
has  already  been  considered  in  the  section  of  Symptomatology. 
The  general 'subject  of  the  treatment  of  toxemias  of  pregnancy 
will  be  considered  under  two  main  divisions:  That  relating  to 
the  disorders  of  the  early  months  as  manifested  by  excessive 
vomiting  and  that  dealing  with  toxemias  associated  with  the  lat- 
ter months  and  generally  known  as  eclampsia. 


TREAMENT  OF  HYPEREMESIS 

Physical  Examination. — A  patient  presenting  herself  with  a 
history  of  vomiting  associated  with  amenorrhea,  should  first  of  all 
be  subjected  to  a  careful  general  physical  examination.  After  this 
has  been  done  and  the  condition  of  the  heart,  lungs,  kidneys, 
digestive  system,  etc.,  determined,  a  careful  pelvic  examination 
should  make  known  the  position  of  the  uterus,  the  condition  of 
the  cervix  and  other  deviations  from  the  normal.  The  association 
of  definite  mechanical  or  pathological  findings  should  prompt 
immediate  attention  to  their  correction.  Malpositions  of  the 
uterus  are  frequently  associated  with  the  nausea  and  vomiting  of 
pregnancy.  If  a  retroverted  uterus  is  found  in  a  primipara  we 
may  accept  this  as  the  congenitally  normal  position  of  the  organ 
and  attempts  at  correction  are  often  a  failure  and  become  very 
distressing  and  painful  until  the  uterus  is  large  enough  to  come 
out  of  the  pelvis.  It  is  unnecessary  to  attempt  the  correction  of 
this  deformity  in  a  woman  in  whom  such  a  position  is  the  normal 
one,  and  we  know  that  in  a  certain  number  of  cases  the  uterus  is 
in  a  retroverted  or  retroflexed  position.  In  a  woman  who  has 
borne  children,  however,  retroflexion  may  be  acquired,  and  if  so, 
it  is  ordinarily  a  simple  matter  to  replace  the  organ,  if  it  is  not 
adherent. 

Retroflexion,  Correction  of. — I  have  not  been  impressed  with 
the  necessity  for  the  correction  of  retroflexion  unless  the  fundus  of  the 


92  TOXEMIAS  OF   PREGNANCY 

uterus  gets  caught  under  the  promontory  of  the  sacrum  in  about  the 
fourth  month  when,  in  addition  to  the  nausea  and  vomiting,  there 
is  usually  present  the  associated  symptom  of  pain.  In  order  to 
relieve  the  uterus  from  its  fixed  position  in  such  cases  it  is  neces- 
sary to  place  the  patient  in  the  knee-chest  posture  and  then,  with 
a  bivalve  speculum  exposing  the  cervix,  the  anterior  lip  is  seized 
with  a  strong  double  tenaculum  forceps  and  by  traction  efforts  an 
attempt  is  made  to  release  the  fundus  from  its  impacted,  position, 
aided  by  the  fingers  in  the  vagina.  Before  doing  this,  the  patient 
should  first  be  advised  to  assume  the  knee-chest  position  at  daily 
intervals  and  not  to  lie  upon  her  back  while  resting.  I  have  seen 
several  cases  in  which  a  retroposed  or  retroverted  uterus  was 
restored  to  an  anterior  position  without  further  manipulation.  A 
uterus  of  this  size  cannot  be  held  in  place  by  a  pessary  with  any 
degree  of  comfort. 

In  the  earlier  months,  however,  if  a  retroversion  is  determined 
to  be  pathological  and  it  is  possible  to  replace  the  organ,  the 
ordinary  retroversion  pessary  may  be  worn  by  the  patient  until 
the  fundus  rises  above  the  pelvic  brim.  One  should  exercise  care, 
however,  in  its  introduction,  and  remove  it  at  intervals  of  two  or 
three  weeks  for  cleansing.  If  any  jpain  or  discomfort  results  the 
pessary  must  be  removed  at  once  and  preferably  no  further 
attempts  made  to  use  it  for  this  purpose.  The  patient  should  also 
be  directed  to  douche  at  least  twice  a  week,  with  warm  water  contain- 
ing a  teaspoonful  of  powdered  borax  to  two  quarts,  employing  for  the 
purpose  a  glass  douche  nozzle  which  is  thoroughly  cleansed  after  use 
and  kept  in  a  folded  fresh  towel.  It  is  advisable,  especially  where  a 
vaginal  discharge  is  present,  to  make  a  visual  examination  of  the 
cervix  through  a  bivalve  speculum. 

Hyperemesis  has  been  attributed  to  any  one  of  a  number  of 
cervical  lesions,  including  stenosis,  erosions,  chronic  inflamma- 
tions of  the  canal,  and  lacerations. 

Stenosis  of  Cervical  Canal. — Dilatation  of  the  canal  with  grad- 
uated sounds  at  daily  intervals  has  been  suggested,  the  dilatation 
being  carried  on  until  relief  from  symptoms  results.  It  is  asserted 
that  this  procedure  is  harmless  and  efficient,  yet  I  hesitate  to 
recommend  it  for  two  reasons:  In  the  first  place,  the  dilatation 
of  the  cervical  ring  will  undoubtedly  tend  to  a  relaxation  of  the 
entire  muscular  structure  of  the  uterus  as  we  see  it  during  the 
ordinary  dilatation  and  curettage  for  other  purposes.  If  a  sound 


TREATMENT  93 

is  introduced  into  a  nonpregnant  uterus  before  dilatation  of  the 
cervix  and  again  after  this  procedure,  a  difference  in  the  measure- 
ments of  the  cavity  is  at  once  apparent.  It  seems  to  me  that  this 
relaxation  can  also  occur  during  the  prophylactic  stretching  of  the 
cervix  recommended  for  the  relief  of  nausea  and  vomiting  of 
early  pregnancy,  and  that  unfortunate  results  may  follow.  In  the 
second  place,  the  passage  of  a  dilating  instrument,  unless  great 
care  is  observed  in  cleansing  the  region  of  the  external  os,  may 
introduce  infectious  organisms  into  the  canal  itself  and  if  these 
should  pass  beyond  the  level  of  the  internal  os,  infection  of  the 
endometrium  or  chorion  may  result,  with  possible  expulsion  of 
the  ovum  or  its  death. 

Cauterization  of  Cervical  Erosions. — The  presence  of  cervical 
"erosions,"  or  so-called  ulcerations,  has  been  given  a  place  in  the 
etiology  of  the  vomiting  in  the  early  months  of  pregnancy. 
Whether  we  can  attribute  a  direct  reflex  origin  to  the  erosion  due 
to  irritation  of  the  nerve  endings  in  the  cervix,  or  whether  the 
presence  of  such  discrepancies  in  the  mucous  membrane  of  the 
cervix  results  in  a  low  grade  of  sepsis  from  absorption,  is  unde- 
cided. At  any  rate,  the  mere  finding  of  such  a  lesion  should  lead 
to  its  correction,  and  this  can  be  done  in  most  instances  with  bene- 
fit to  the  patient.  Whether  this  be  by  direct  effect  on  the  patho- 
logical process  or  for  psychic  reasons  need  not  be  considered. 
Cauterization  of  the  eroded  area  with  nitrate  of  silver  at  intervals 
of  several  days,  together  with  the  application  of  a  depleting 
tampon,  has  never,  in  my  hands,  had  any  deleterious  effect  in  so 
far  as  abortion  is  concerned.  Patients  experience  a  great  deal  of 
relief  from  the  disagreeable  and  irritating  discharge  which  usually 
is  associated  with  this  lesion  and  which  becomes  worse  during 
pregnancy  because  of  the  increased  hyperemia  of  the  cervix. 
Lacerations  cannot,  of  course,  be  done  away  with  at  this  time  for 
obvious  reasons,  but  this  need  not  preclude  the  treatment  of  the 
associated  erosion,  although  the  effect  may  only  be  temporary. 

General  Hygiene. — Of  course  the  local  treatment  should  go 
hand  in  hand  with  general  hygienic  measures,  including  some  that 
are  to  be  directed  particularly  to  the  symptoms.  In  order  to  treat 
intelligently  a  given  case  we  must  take  into  consideration  the 
degree  to  which  the  vomiting  has  progressed.  In  the  milder  cases 
general  medical  measures  often  suffice,  and  these  are  so  well 
known  that  it  is  necessary  merely  to  enumerate  them  without 


94  TOXEMIAS  OF  PREGNANCY 

going  into  particular  details,  although  mention  may  be  made  of 
certain  therapeutic  procedures  that  are  found  to  produce  excellent 
results.  In  the  first  place,  the  patient  must  be  given  a  certain 
amount  of  rest  during  the  twenty-four  hours  in  addition  to  the 
usual  sleeping  period.  As  patients  are  very  apt,  in  mild  degrees 
of  this  disorder,  to  experience  the  nausea  on  arising,  it  is  advisable 
to  have  them  take  nourishment  on  awakening  and  then  to  go  back 
to  bed  for  another  hour  at  least,  lying  on  the  right  side  if  possible, 
so  as  to  facilitate  the  emptying  of  the  stomach.  This  early  break- 
fast should  consist  of  toast,  zwieback,  and  a  cup  of  tea,  or  the 
proverbially  accepted  black  coffee. 

The  patient  should  be  directed  to  get  up  an  hour  or  two  after 
this  early  meal  and  proceed  to  dress  in  a  leisurely  manner,  after 
which  a  second  breakfast  may  be  taken  of  whatever  she  desires. 
As  a  rule  the  nausea  which  follows  this  meal  disappears  within  a 
short  time,  or,  if  vomiting  does  take  place,  the  entire  meal  may 
not  be  evacuated.  In  many  patients  there  is  no  further  dis- 
turbance during  the  day,  but  others  experience  nausea  and  occa- 
sional periods  of  vomiting  at  any  time  during  the  waking  hours. 
Another  rest  period,  if  this  can  be  secured  in  the  middle  of  the 
day,  is  often  advantageous.  Meals  should  be  taken  at  regular 
intervals  and  it  would  be  better  for  the  usual  quantities  to  be 
divided  so  that  the  patient  eats  not  three,  but  six  or  seven,  times 
a  day. 

In  many  women  the  production  of  saliva  seems  to  have  a 
favorable  effect,  and  such  patients  may  be  directed  to  carry  about 
with  them  hard  sweet  crackers,  raisins,  chocolate,  or  similar 
articles  to  chew  at  intervals  between  the  regular  meals.  Chewing 
gum  also  seems  to  be  of  value  at  this  time.  Ordinarily,  even  if 
vomiting  occurs  two  or  three  times  during  the  twenty-four  hours, 
no  loss  in  weight  results  because  at  least  some  of  the  food  is 
retained  and  digested.  In  a  more  severe  grade  of  this  disorder, 
however,  the  quantity  of  vomited  material  varies  from  one  half  to 
the  entire  amount  ingested,  and,  in  such  cases,  unless  the  process 
is  stopped,  starvation  with  its  attending  bad  effects  results.  It 
may  be  advisable  to  have  such  patients  remain  in  bed  the  greater 
part  of  the  day  in  a  well-ventilated,  quiet  room,  until  a  balance  in 
the  food  requirements  has  been  obtained.  In  this  type  of  the 
disease  the  so-called  carbohydrate  scheme  of  dieting  as  worked 
out  by  a  number  of  investigators  is  of  great  value. 


TREATMENT  95 

Diet  Schedule. — I  have  been  in  the  habit  of  furnishing  patients 
with  mild  vomiting  with  a  diet  schedule  as  follows:  They  are 
directed  to  avoid  all  meat,  soup,  and  fats  during  the  period  of 
vomiting  and  to  subsist  entirely  on  cereals,  stewed  fruits,  fresh 
vegetables  and  breadstuffs,  taking  six,  rather  than  the  usual  three, 
daily  meals.  From  one  to  three  pints  of  boiled  water  in  which  two 
or  three  teaspoonfuls  of  milk  sugar  are  dissolved  must  be  taken 
during  teach  twenty-four-hour  period.  If  there  is  a  complaint  of 
"acid  stomach,"  the  patient  in  addition  should  take  a  teaspoonful 
of  bicarbonate  of  soda  in  a  glassful  of  water  on  retiring.  Sound 
sleep  is  favored  by  taking  a  warm  bath  before  retiring. 

Corpus  Luteum  Extract. — If  the  above  directions  do  not  help 
the  condition  the  patient  is  to  report  at  once.  At  this  time  I 
have  occasionally  found  the  hypodermic  injection  of  corpus 
luteum  extract  useful,  although  I  am  not  prepared  to  state 
whether  the  effect  is  really  due  to  the  drug  or  to  the  mental  state 
induced  by  its  administration.  At  any  rate  we  may  credit  Dr.  J.  C. 
Hirst  of  Philadelphia  with  the  popularization  of  a  remedy,  the 
results  from  which  seem  to  give  us  a  fair  basis  for  hope  in  some 
cases.  As  he  found  that  almost  90  per  cent  of  his  series  of 
unselected  cases  were  favorably  influenced,  he  may  be  justified  in 
claiming  that  the  lack  of  normal  corpus  luteum  absorption  is  a 
factor  in  the  nausea  of  pregnancy,  and  that  therefore  it  can  be 
relieved  by  a  hypodermic  or  intramuscular  injection  of  the 
extract.  In  the  cases  in  which  it  has  been  of  benefit,  I  found  that 
daily  injections  for  a  period  of  a  week,  or  on  alternate  days  for  a 
period  of  two  weeks,  seem  to  give  the  best  results. 

An  array  of  specific  drugs  has  been  recommended  to  over- 
come the  nausea  of  pregnancy,  including  cerium  oxylate,  dilute 
carbolic  acid,  cocain,  bismuth,  pepsin,  etc.,  and  while  in  isolated 
cases  they  seem  to  do  good,  the  results  are  usually  unsatis- 
factory and  much  time  may  be  lost  while  trying  them  out. 
Since  the  toxic  origin  of  hyperemesis  has  been  generally  admitted, 
the  employment  of  drugs  for  the  purpose  has  largely  been  aban- 
doned. 

Laxatives  are  usually  indicated,  and  it  is  necessary  to  pre- 
scribe them  in  pill  form  to  favor  retention,  although  in  the 
severer  cases  even  this  is  ineffective.  The  extract  of  cascara  in  5 
grain  doses  alone,  or  combined  with  belladonna,  tincture  of  nux 
vomica  or  aloes,  is  the  most  effective  laxative  and  preferably 


96  TOXEMIAS   OF   PREGNANCY 

should  be  given  on  retiring,  supplemented  by  a  soapsuds  enema  in 
the  morning. 

The  use  of  the  heavier  mineral  oils  which  have  been  so  much 
in  vogue  during  recent  years  is  unsatisfactory  in  hyperemesis,  as 
the  patients  demur  against  the  swallowing  of  such  large  doses 
and  the  results  are  uncertain.  An  occasional  half-ounce  dose  of 
castor  oil,  if  the  patient  can  take  it,  is  valuable  and  likewise  small 
doses  of  calamel  given  in  doses  of  from  *4  to  y2  a  grain  at  half- 
hour  intervals  until  a  total  of  2  or  3  grains  is  taken.  Unfor- 
tunately, calomel  must  be  followed  by  a  saline  the  next  morning, 
and  it  is  often  difficult  for  patients  to  swallow  such  a  dose  on 
getting  up.  In  the  severer-  cases,  where  jaundice  is  present  and 
possible  necrosis  of  the  liver  cells,  calomel  is,  of  course,  contra- 
indicated. 

Prognosis. — It  is  usually  possible  with  the  methods  of 
handling  these  cases  as  outlined  above,  to  carry  a  patient  through 
the  early  months,  and,  if  her  mental  condition  can  be  favorably 
influenced  and  her  patience  developed,  she  can  be  assured  that  the 
vomiting  will  cease  at  the  expiration  of  the  third,  or  not  later  than 
the  fourth,  month  of  her  pregnancy.  I  have  seen  numerous  cases 
in  which  this  has  occurred  and  the  knowledge  of  the  fact  has 
buoyed  up  many  a  patient  until  the  end  of  the  period  stated.  Why 
the  vomiting  should  cease  at  the  expiration  of  a  time  limit  is  not 
yet  explained,  but  as  a  clinical  observation  it  is  well  attested  by 
numerous  cases. 

We  may  assume  that  in  the  degree  of  vomiting  referred  to 
there  is  little  or  no  pathological  change  in  the  essential  organs  of 
elimination  such  as  the  liver  and  kidneys,  but  we  must  be  very 
careful  to  differentiate  these  mild  cases  of  vomiting  from  those 
which  may  be  called  pernicious  in  which,  as  described  in  the  sec- 
tion on  symptomatology,  the  patient  is  unable  to  retain  any  food 
at  all,  does  not  respond  to  the  methods  of  treatment  described, 
loses  very  rapidly  in  flesh  and  strength  and  may  within  a  short 
time  present  an  appearance  of  extreme  emaciation.  In  such  cases 
we  are  dealing  with  a  very  serious  condition  that  may  require  our 
utmost  efforts  to  overcome.  It  is  essential  to  bear  in  mind  that 
we  are  dealing  with  a  toxemia  due  to  perverted  function  and  that 
by  our  treatment  we  must  satisfy  certain  well-defined  needs,  which 
may  be  considered  in  turn. 

First  and  foremost,  the  patient's  nervous  system  must  be  put 


TREATMENT  97 

absolutely  at  rest.  Such  women  are  racked  from  the  constant 
vomiting,  they  are  weak  from  the  lack  of  food  and  irritated  by  the 
numerous  methods  of  treatment  that  have  usually  been  em- 
ployed. Absolute  rest  in  bed  in  a  dark  room  to  which  fresh  air 
can  have  free  access  must  be  insisted  upon  and  the  visits  of  rela- 
tives and  friends  forbidden.  The  patient  should  be  placed  in 
charge  of  a  capable  nurse  who  is  to  be  made  responsible  for  the 
absolute  carrying  out  of  the  physician's  directions  and  under  no 
circumstances  must  these  be  interfered  with  by  sympathizing 
relatives.  The  administration  of  sedatives  and  narcotics  may  be 
indicated  during  this  period  and  for  this  purpose  the  hypodermic 
administration  of  morphine  in  ^4-grain  doses,  together  with 
atropin  (1/150  gr.),  should  be  employed  to  secure  the  much 
needed  sleep.  Chloral  hydrate  in  doses  of  from  20  to  40  grains, 
and  the  mixed  bromids  in  doses  of  from  30  to  60  grains  by  rectum  in 
one  of  the  nutrient  enemas  are  also  very  efficient.  The  patient 
must  not  be  allowed  to  read  or  to  tax  her  strength  in  any  manner. 

The  next  condition  to  be  fulfilled  is  to  supply  the  dehydrated 
tissues  with  water.  The  giving  of  water  by  mouth  is  often  impos- 
sible; in  such  cases  it  must  be  given  by  rectum,  under  the  skin,  or 
into  a  vein,  depending  on  the  severity  of  the  individual  case.  The 
third  desideratum  is  the  supplying  of  nutrients,  and  as  mouth 
feeding  in  such  patients  is  impossible,  the  necessary  food  must  be 
given  by  rectum.  Fourth,  the  emunctories  must  be  thoroughly 
attended  to.  Warm  baths  or  bed  baths  for  the  skin,  an  open,  airy 
room  for  the  lungs,  and  irrigations  for  the  bowels,  must  all  be 
supplied. 

Care,  Routine  of. — A  more  or  less  routine  plan  may  be  out- 
lined as  follows,  to  be  modified  as  the  individual  needs  of  the 
patient  require :  A  quiet,  well-ventilated  room  which  can  be  dark- 
ened, either  in  the  patient's  home  or,  preferably  in  the  hospital, 
and  absolute  rest  in  bed,  with  no  visitors.  Beginning  in  the  morn- 
ing, about  eight  o'clock,  a  cleansing  enema  is  given  with  soapsuds 
to  which  glycerin  may  be  added  in  the  proportion  of  one  half  an 
ounce  to  the  quart.  After  this  has  been  completely  evacuated, 
8  ounces  of  a  5  per  cent  glucose  solution  to  which  from  30  to  60 
grains  of  bicarbonate  of  soda  have  been  added,  is  given  by  rectum. 
This  rectal  infusion  is  repeated  at  twelve,  four,  and  eight  o'clock, 
a  total  of  four  doses  with  32  ounces  of  fluid  and  from  2  to  4  drams 
of  bicarbonate  of  soda.  If  the  skin  is  drv  and  does  not  seem  to 


98  TOXEMIAS   OF   PREGNANCY 

function  well,  a  hot  pack  lasting  from  ten  to  twenty  minutes  may 
be  given  after  the  eight  P.  M.  rectal  infusion.  This  will  usually 
insure  the  distribution  of  the  circulating  blood  under  the  skin, 
bring  about  perspiration,  make  the  body  desirous  of  more  fluid, 
and  induce  a  quiet  sleep.  Nothing  whatever  is  given  by  mouth 
until  the  vomiting  begins  to  lessen,  when  small  doses  of  hot 
water  or  weak  lemonade  may  be  taken,  together  with  a  mouthful 
or  two  of  cracker  or  toast.  The  teeth  should  be  kept  clean  and 
the  tongue  scraped,  as  this  contributes  very  much  to  the  comfort 
of  the  patient.  The  injection  of  fluid  by  rectum  may  usually  be 
kept  up  for  several  days  without  producing  any  irritation,  but  if 
the  rectum  becomes  irritated- the  addition  of  20  drops  of  camphor- 
ated tincture  of  opium  to  each  glucose  instillation  will  obviate  this 
difficulty  and,  moreover,  act  as  a  sedative.  If  the  patient  is  rest- 
less and  cannot  sleep,  15  grains  of  chloral  or  30  grains  of  sodium 
bromid  may  be  introduced  into  the  evening  glucose  instillation. 
The  urine  of  these  patients  often  shows  marked  traces  of 
albumin,  diacetic  acid  and  oxybutyric  acid;  it  is  dark  in  color, 
concentrated  and  of  high  specific  gravity.  It  is  on  this  account 
that  the  alkali  is  given  and  we  may  continue  it  in  doses  suf- 
ficiently large  to  produce  an  alkaline  reaction  in  the  urine.  I 
have  found,  however,  that  more  than  60  grains  of  soda  bicar- 
bonate by  rectum  may  prove  irritating  and  in  its  place  a  pint 
or  more  of  Kalak  water  may  be  used,  or  one  and  one-half 
ounces  of  milk  of  magnesia.  Salt  solution  must  under  no  con- 
sideration be  employed,  as  the  excretion  of  the  salt  contents 
through  the  kidneys  only  increases  the  renal  irritability  or  the 
nephritis  which  may  already  be  present.  In  cases  in  which 
dehydration  of  the  body  is  more  advanced  and  in  which  the 
acidosis  is  not  cleared  up  within  a  day  or  two,  the  subcutaneous 
injection  of  sterile  decinormal  soda  bicarbonate  solution  under  the 
breasts  may  be  employed,  or  a  solution  of  glucose  may  be  injected 
intravenously,  which  in  some  instances  has  been  recommended  as 
strong  as  25  per  cent.  In  my  own  experience  I  have  hesitated 
to  use  this  stronger  and  more  viscid  solution  and  believe  that 
equally  good  results  will  be  obtained  from  a  5  per  cent  solution. 
Even  in  extreme  cases  of  emaciation,  glucose  may  be  given  intra- 
venously and  I  have  seen  excellent  results  in  patients  in  whom  8 
ounces  were  given  daily  for  two  or  three  days  in  succession.  A 


TREATMENT  99 

more  detailed  reference  to  use  of  glucose  infusions  will  be  found 
later  on  in  this  chapter. 

Thirst,  Relief  of. — Women  who  complain  bitterly  of  the 
thirst  and  yet  vomit  as  soon  as  any  water  is  taken  will  be 
relieved  of  this  distressing  condition  within  twenty-four  hours 
after  the  instillation  of  the  fluid  by  rectum  has  been  begun.  It  is 
unnecessary  to  employ  any  drug  administration  at  this  time, 
although  the  use  of  the  corpus  luteum  extract  by  intramuscular 
injection  may  be  resorted  to.  If  used  in  the  severe  cases  it  should 
be  given  at  least  twice  daily  to  obtain  any  possible  favorable 
effect. 

It  will  be  noted  that  in  the  above  method  of  treating  hyper- 
emesis  no  attempt  is  made  to  introduce  nutrient  materials  in  the 
enemas  such  as  have  been  so  generally  used  for  the  purpose, 
including  eggs,  peptonized  milk,  beef  extracts,  etc.  It  seems  to 
me  sufficiently  well  demonstrated  that  the  rectum  fails  to  absorb 
any  such  materials  even  in  health,  and  their  administration  in  an 
emaciated  patient  can  certainly  be  of  no  avail.  I  believe,  more- 
over, that  the  absorptive  function  of  the  rectal  mucosa  is  inter- 
fered with  by  the  introduction  of  these  materials  and  that  the 
necessary  ingestion  of  water  is  thus  prevented.  I  have  given  up 
such  methods  entirely  and  believe  better  results  follow  the  use  of 
water  alone  without  any  of  the  nutrient  substances  formerly  so 
much  in  vogue. 

Induction  of  Abortion — WHEN  ADVISABLE. — Although  a  con- 
siderable number  of  cases  are  improved  by  this  treatment,  it  must 
not  be  persisted  in  if  the  patient  fails  to  show  any  change  for  the 
better  within  a  few  days,  and  if  the  acidosis,  as  shown  by  daily 
urine  examinations,  does  not  improve;  if  vomiting  of  bile-stained 
fluid  or  coffee-ground  material  occurs;  if  the  yellow  staining  of 
the  skin  and  sclera  persists  or  grows  deeper;  if  the  blood-pressure 
falls  day  by  day;  if  the  urine  becomes  less  in  amount  and  of  a 
greater  specific  gravity — all  temporizing  methods  should  be 
stopped  and  the  uterus  emptied.  Too  many  women  are  carried 
along  from  day  to  day  in  the  hope  that  one  or  the  other  method 
of  treatment  will  pull  them  through  and  then,  when  an  abortion 
is  finally  attempted,  the  patient  is  too  weak  to  survive  its  effects. 

We  can  always  feel  that  the  induction  of  abortion  is  justified  in 
such  cases  because,  if  the  woman  recovers,  she  may  usually  be 
guided  through  another  pregnancy  with  proper  care.  I  have  had 


100 


TOXEMIAS  OF   PREGNANCY 


a  personal  experience  with  several  patients  who,  when  pregnant 
for  the  first  time,  developed  a  hyperemesis  which  grew  rapidly 
worse  notwithstanding  all  treatment,  in  whom  a  rapid  recovery 
followed  the  emptying  of  the  uterus  and  in  their  next  attempt  at 
a  pregnancy  no  harmful  consequences  whatever  followed.  The 
induction  of  abortion  should  therefore  not  be  delayed  beyond  the 
limits  referred  to  above,  and  when  done  it  must  be  carried  out 
under  the  most  careful  auspices.  This  is  essential  because  a 
degree  of  infection  which  would  not  affect  an  ordinary,  healthy 
woman  might  prove  fatal  in  a  case  of  this  kind. 

METHODS  OF  ABORTION. — As  little  shock  as  possible  must  be  pro- 
duced in  the  abortion,  and  it  is  therefore  advisable  to  precede  the  clear- 


FIG.  23. — BLOOD-PRESSURE  CHART  FROM  A  CASE  OF  ECLAMPSIA  IN  WHICH  RAPID 
DELIVERY  WAS  DONE  AND  VERATRUM  VIRICE  WAS  GIVEN.  Shows  a  fall  of  105 
millimeter  in  thir-yfive  minutes  (Bailey) . 

ing  out  of  the  uterus,  especially  if  we  are  dealing  with  a  primipara,  by 
a  preliminary  packing  of  the  cervix  for  twenty-four  hours  with  a 
narrow  strip  of  gauze.  This  softens  up  the  cervix,  can  be  done 
without  anesthesia  and  makes  the  instrumental  dilatation  twenty- 
four  hours  later  very  much  easier.  In  pregnancies  which  have 
reached  the  third  month  the  membranes  may  also  be  ruptured,  as 
this  at  once  relieves  intra-uterine  tension  and  tends  to  spontane- 
ous abortion.  It  is  not  unusual  to  find  when  the  gauze  is  removed 
that  the  cervix,  even  in  primiparae,  is  so  softened  and  dilated  that 
the  ovum  projects  from  it.  The  patient  is  prepared  as  for  dilata- 
tion and  curettage  twenty-four  hours  after  the  initial  introduction 
of  gauze.  The  operation  can  usually  be  done  under  gas-oxygen 
anesthesia  preceded  by  a  hypodermic  of  ^4  of  a  grain  of  morphin. 


TREATMENT 


101 


Chloroform  is  absolutely  contra-indicated  on  account  of  its  effect 
on  the  liver;  and  ether,  while  less  dangerous,  is  unnecessary, 
requires  more  time  for  administration  and  may  produce  a  dele- 
terious effect  on  the  kidneys  (Figs.  23,  24,  25).  With  the  patient  in 
the  lithotomy  position,  or  better  still,  with  the  legs  held  by  two  assist- 
ants, the  vulva  is  quickly  shaved  if  this  has  not  been  done  before  the 
packing  is  introduced,  and  the  surrounding  skin  surfaces  and  the 


Fe6.20 
7PM  8      0       IO 


Hours 

12    iam  2 


Feb.2/ 

•4        5      6 


& 


ii.zop.rr 


-CU, 


FIG.  24. — BLOOD-PRESSURE  CHART  FROM  A  PRE-ECLAMPTIC  CASE,  SHOWING  RAPID  FALL 
(145  MILLIMETER  WITHIN  THREE  HOURS)  AFTER  THE  ADMINISTRATION  OF  VERA- 
TRUM  VIRIDE  ALONE  (Bailey). 

vagina  painted  with  a  3^  per  cent  tincture  of  iodin.  The  cervix 
is  then  exposed  through  a  speculum,  seized  with  a  double  tenac- 
ulum  forceps,  and,  if  the  dilatation  is  insufficient,  it  may  be  com- 
pleted with  the  graduated  sounds.  A  branched  dilator  is  not  ad- 
visable because  of  the  possibility  of  tearing  the  softened  cervix. 
In  fact,  a  more  complete  and  satisfactory  dilatation  is  possible 
with  the  Hegar  or  a  similar  instrument.  The  fruit-sac  can  usually 


102 


TOXEMIAS  OF  PREGNANCY 


be  seized  with  an  ordinary  Foster's  sponge-holder  and  removed. 
If  it  does  not  come  away  in  its  entirety,  the  clearing  out  of  the 
uterine  cavity  should  be  readily  and  quickly  done  with  a  sponge- 
holder,  or  with  a  large  and  not  very  sharp  curet,  after  which  the 
cavity  is  wiped  dry  with  gauze  and  packed  with  a  strip  of  plain 
gauze  one  inch  wide.  Such  patients  do  not  stand  the  loss  of  blood 
well  and  it  is  desirable,  therefore,  to  extract  as  much  of  the  ovum 
in  one  piece  as  possible.  The  bleeding  can  also  be  reduced  by  a 
hypodermic  injection  of  i  cubic  centimeter  of  pituitrin  just  before 
the  dilatation  is  begun,  which  controls  the  bleeding  during  the 
operation  and  the  gauze  pack  exercises  a  similar  function  imme- 
diately afterwards. 

/9/0. 


200 


180 
170 
160 
150 
140 
/30 
120 

110 
100 


abr 


s.  so  b  r 


25 


;op.n. 


tipr.  i 


"S 


io.a. 


apr.zr. 


FIG.  25. — BLOOD-PRESSURE  CHART  FROM  A  CASE  OF  ECLAMPSIA  WITH- TWINS,  SHOWING 
TEMPORARY  REDUCTION  AFTER  DELIVERY  BUT  WITH  FINAL  RECOVERY  (Bailey). 

VAGINAL  HYSTEROTOMY  IN  PRIMIPAR^E.  • — In  primiparse  with 
long,  rigid  cervices,  in  which  dilatation  would  ordinarily  be  a  slow 
process,  and  who  are  in  bad  general  condition  from  exhaustion,  a 
rapid  and  satisfactory  emptying  of  the  uterus  may  be  done  by  a 
vaginal  hysterotomy,  particularly  if  the  pregnancy  has  reached 
the  third  month.  In  such  cases  the  preliminary  gauze  pack  is  not 
needed.  The  patient  is  prepared,  anesthetized  with  gas-oxygen 
followed  by  a  small  amount  of  ether;  the  cervix  is  seized  and 
pulled  down  and  a  transverse  incision  made  at  the  bladder  junc- 
tion in  the  anterior  vaginal  vault.  It  is  usually  not  necessary  to 
strip  back  the  bladder  very  far.  The  anterior  lip  of  the  cervix  is 
then  cut  through  in  the  median  line  to  the  level  of  the  internal  os, 
which  gives  sufficient  room  for  the  evacuation  of  the  fruit-sac. 


TREATMENT  103 

The  cervical  incision  is  then  quickly  closed  with  several  inter- 
rupted chromic  gut  sutures,  followed  by  suture  of  the  mucous 
membrane  wound  in  the  vaginal  fornix.  The  uterine  cavity,  in- 
cluding the  vagina,  is  firmly  packed  with  narrow  strip  (from  }4 
to  y&  inch)  of  iodoformized  or  plain  gauze.  If  the  fruit-sac  can- 
not be  removed  in  its  entirety,  a  rapid  curetting  of  the  uterine 
cavity  may  be  done.  The  packing  is  essential  to  stop  the  bleeding 
from  the  uterus  or  the  operative  wounds,  as  the  patient  needs  to 
conserve  every  drop  of  blood  at  this  time. 

SHOCK. — Shock  is  common  in  these  cases,  but  may  usually  be 
avoided  by  instituting  the  rectal  glucose  feedings  (8  ounces  of  a 
5  per  cent  solution)  every  four  hours  as  soon  as  the  patient  is 
returned  to  bed.  I  have  found  it  advisable  to  keep  up  the  glucose 
infusions  for  five  days  or  more  in  lessened  amounts.  When  the 
patient  is  greatly  emaciated  a  hypodermoclysis  of  a  pint  of  5  per 
cent  sugar  solution  may  be  given  under  each  breast,  or  8  ounces 
of  the  solution  carefully  sterilized,  may  be  injected  intravenously. 
When  shock  is  marked  the  intravenous  injection  of  a  stronger  glucose 
solution  (25  per  cent)  to  which  gum  acacia  has  been  added,  as  recom- 
mended by  Farrar,  is  of  great  value  and  I  have  employed  it  with 
excellent  results  in  several  cases. 

Before  an  operative  procedure  in  a  toxic  patient,  whether  in 
the  early  or  late  months  of  pregnancy,  the  acidosis  which  is 
usually  present  must  be  combated  by  the  administration  of  an 
alkali,  preferably  sodium  bicarbonate.  According  to  Palmer  and 
Van  Slyke,  0.5  grain  of  the  latter  for  each  forty-two  pounds  of 
body  weight  will  raise  the  carbon  dioxid  combining  power  of  the 
blood  i  per  cent  by  volume.  Killian  recommends  its  adminis- 
tration intravenously  in  a  4  per  cent  solution,  which  can  be  given 
before  operation  and  then  continued  by  rectal  infusions  until 
recovery  takes  place. 

The  lowered  blood-pressure  which  is  usually  found  must  be 
combated  by  the  administrated  of  adrenalin  in  doses  of  from  10  to 
20  minims  by  hypodermic,  or  40  minims  may  be  included  in  the 
glucose  rectal  infusion.  The  body  heat  must  also  be  conserved 
and  chilling  of  the  patient  avoided  during  operation  and  immediately 
afterwards.  In  a  great  many  cases  death  results  within  twenty-four 
hours,  or  later,  due  not  only  to  the  extreme  degree  of  shock  and 
exhaustion,  but  to  the  development  of  various  contribut°ry  causes — 


io4  TOXEMIAS   OF   PREGNANC.Y 

pneumonia,  embolism,  infection — all  of  which  are,  of  course,  to  be 
treated  symptomatically. 

Hospital  Care. — The  treatment  of  hyperemesis  of  pregnancy 
outlined  here  must  be  varied  not  only  to  suit  the  individual  case 
but  must  also  be  adapted  to  the  surroundings  under  which  it  has 
to  be  carried  out.  In  private  homes  the  necessary  isolation  and 
quiet  is  often  difficult  to  obtain,  and  unless  this  can  be  satisfac- 
torily done,  it  is  better  to  send  the  patient  to  a  hospital.  The 
milder  grades  of  the  disturbance  can  usually  be  managed  without 
recourse  to  hospital  discipline,  but  as  soon  as  the  vomiting 
becomes  to  any  degree  extreme  and  uncontrollable,  a  transfer  to 
the  hospital  is  not  only  desirable  but  necessary.  The  change 
from  bad  to  worse  may  take  place  very  rapidly,  and,  as  a  general 
rule,  the  emptying  of  the  uterus  cannot  be  as  safely  done  in  the 
home  as  under  proper  hospital  surroundings. 

Supplementary  Measures. — The  scheme  of  treatment  for  per- 
nicious vomiting  as  described  in  the  preceding  paragraphs  may 
be  supplemented  by  recourse  to  a  variety  of  other  measures  which 
are  reported  in  the  literature  on  the  subject.  I  do  not  propose 
to  include  the  various  preparations  and  drugs  recommended 
merely  for  the  specific  purpose  of  correcting  nausea  or  vomiting, 
for  their  use  is  more  or  less  empirical  and  without  regard,  in  most 
instances,  to  any  possible  underlying  etiological  factor.  It  would 
be  impossible,  in  fact,  to  enumerate  them  in  the  limits  of  these 
pages  and  no  good  purpose  would  be  served.  We  may,  however, 
refer  briefly  to  certain  measures  for  the  relief  of  this  condition 
which,  to  some  extent,  have  a  rational  basis  for  their  use. 

SERA  AND  GLAND  EXTRACTS. — Normal  Human  Blood  Serum. — 
The  assumption  that  the  toxemia  which  underlies  excessive  vomiting  is 
due  to  circulating  materials  in'the  blood  of  the  patient,  which  are  either 
not  present  in  nonpregnant  individuals  or  may  be  rendered  inert 
by  the  blood  of  the  latter,  has  led  to  the  employment  of  normal 
human  blood  serum  by  several  investigators.  Thus  Fieux  was 
probably  the  first  to  suggest  these  injections  and  Bondy,  some- 
what later,  presented  his  observations  on  21  cases  of  hyperemesis. 
He  was  led  to  use  serum  after  studying  the  findings  from  the 
Abderhalden  tests,  according  to  which  it  is  assumed  that,  shortly 
after  conception  takes  place,  substances  circulate  in  the  maternal 
organism  which  may  be  regarded  as  foreign  matter.  Under  cer- 
tain circumstances,  not  yet  determined,  these  substances  can 


TREATMENT  105 

upset  the  perfect  balance  of  the  organism  and  thus  produce  vomit- 
ing among  other  symptoms.  The  activity'of  these  substances  in 
the  organism  is  to  be  traced  either  to  their  increased  formation  or 
to  the  diminished  combination  with  antidotes,  resulting  in  a  con- 
dition of  toxemia,  and  their  effect  may  subsequently  be  increased 
by  psychic  influences,  neuropathic  disposition  or  pathological 
processes  in  the*genital  organs  themselves.  The  dosage  in  these 
cases  is  from  10  to  15  cubic  centimeters  of  serum  from  a  normal, 
pregnant  woman  with  a'negative  Wassermann,  by  injection  into 
the  back  muscles  one  or  more  times  daily. 

Horse  serum  and  Ringer's  solution  have  also*  been  employed 
for  hyperemesis  with  reports  of  a  similar  effect. 

Negative  Results. — Among  the  negative  results  reported  we  find 
an  observation  by  Rubeska  in  two  cases.  In  the  first  case,  10 
cubic  centimeters  of  normal  pregnancy  serum  was  injected  into 
the  gluteal  region,  and  this  amount  was  given  three  times  on  the 
next  d^y  but  without  result,  so  that  abortion  was  required.  In 
the  second  case,  40  cubic  centimeters  were  given  into  the  median 
basilic  vein  and  two  days  later  an  equal  quantity  in  another  vein, 
together  with  20  cubic  centimeters  subcutaneously.  Vomiting 
seemed  to  be  slightly  improved  for  a  short  time,  but  on  becoming 
worse  the  next  day  another  injection  of  55  cubic  centimeters  was 
given  into  the  v^ein  and  15  cubic  centimeters  intramuscularly.  No 
result  was  obtained  and  abortion  had  to  be  induced.  J.  Whitridge 
Williams  states  that  he  has  also  been  unable  to  confirm  the  claims 
advanced  for  these  serum  injections  and  believes  that  any  good 
results  which  followed  may  be  attributed  to  suggestion. 

Fetal  Serum. — During  the  course  of  an  investigation  on  the  effect 
of  fetal  serum  on  the  onset  of  labor,  Rongy  observed  a  favorable 
effect  in  a  patient  with  Well  marked  symptoms  of  impending 
eclampsia.  By  analogy  serum  from  the  cord  blood  v/as  used  in 
four  severe  vomiting  cases  with  apparently  favorable  results. 
From  10  to  15  cubic  centimeters  were  given  intramuscularly  at 
intervals  of  several  days  and  in  one  rather  severe  case  it  was  given 
into  a  vein.  In  all  these  patients  the  vomiting  finally  ceased,  but 
the  severity  of  the  symptoms  as  described  by  the  author  makes 
one  hesitate  about  resorting  to  the  procedure  at  the  expense  of 
valuable  time  lost  in  emptying  the  uterus. 

Placental  Extracts. — From  the  use  of  fetal  serum  it  seems  but  a 
step  to  the  employment  of  the  placental  extract  and  we  find  this  pro- 


106  TOXEMIAS  OF   PREGNANCY 

cedure  advocated  by  Gary,  who  bases  the  administration  of  this  sub- 
stance on  certain  animal  experiments  made  by  A.  H.  Curtis.  The  latter 
found  that  injections  of  placental  extracts  in  rabbits  and  guinea  pigs 
increased  the  resistance  from  immunity  to  such  an  extent  that  the 
existing  balance  was  altered,  causing  death  and  lysis.  Gary  then 
reasoned  that  if  toxemia  of  early  pregnancy  is  due  to  a  lowered 
immunity  to  the  growth  of  the  syncytium,  the  placenta  may 
stimulate  by  acting  as  an  antigen.  Moreover,  if  the  proteolytic 
ferment  is  lower  than  normal,  as  demonstrated  by  the  negative 
Abderhalden  reaction,  the  desiccated  placenta  may  increase  the 
ferment  content  of  the  blood.  Finally,  if  the  placenta  is  an 
internal  secretory  gland,  its  administration  may  increase  the 
activity  of  the  thyroid  and  adrenals  and  thus  hasten  the  oxidation 
of  partial  protein  by  throwing  split  products  into  the  circulation. 

Gary  treated  13  cases  of  vomiting  at  different  periods  of  gesta- 
tion with  the  placental  extract.  Of  the  13,  7  stopped  vomiting 
within  a  day  or  two  and  the  nausea  soon  disappeared ;  2  improved  and 
remained  fairly  free  from  nausea;  in  2  the  results  were  not  satisfac- 
tory ;  the  other  2  were  lost  sight  of.  In  a  series  of  6  cases  treated  by 
an  associate,  3  showed  good  results  with  varying  success  in  the  other  3. 
The  placental  extract  was  given  by  mouth  in  5-grain  capsules  three 
times  daily,  over  a  period  of  from  ten  to  twelve  days.  In  one  of  the 
series,  a  woman  with  pre-eclamptic  toxemia,  a  stillbirth  resulted, 
although  the  toxic  symptoms  of  the  mother  became  no  worse  during 
the  administration  of  the  extract  and  the  blood-pressure  fell  about 
twenty  points. 

In  connection  with  this  theory,  attention  must  be  called  to  the  fact 
that,  in  so  far  as  cellular  activity  is  concerned,  the  placenta  is  merely 
active  during  the  stage  of  trophoblastic  development  which  is  the  only 
time  during  which  a  hormone  or  other  secretory  material  is  formed.  A 
placental  extract  desired  for  therapeutic  purposes  should,  according  to 
Culbertson,  be  prepared  from  early  placenta  or  early  chorionic  villi, 
which,  in  the  human  female,  would  have  to  be  before  the  fourth  month. 
It  has  been  shown  experimentally  that  the  physiological  action  of  the 
trophoblast  is  identical  with  that  of  the  corpus  luteum  of  preg- 
nancy, which  may  explain  the  favorable  effects  claimed  for  the 
latter  when  administered  for  the  relief  of  hyperemesis.  Unfor- 
tunately, hormones  do  not  produce  antibodies  and  cannot  be 
demonstrated  by  any  complement  fixation  tests.  The  entire  sub- 
ject is  surrounded  by  so  many  uncertainties  that  further  obser- 


TREATMENT  107 

vations  are  demanded  before  any  recommendations  can  be  made. 

ADRENALIN  CHLORID. — Adrenal  insufficiency  as  a  factor  in  the 
production  of  the  vomiting  of  pregnancy  was  first  advanced  by 
Rebaudi  and  has  since  been  discussed  by  others.  Zuloaga  declares 
that  such  adrenal  insufficiency  can  be  diagnosed  by  the  fact  that  a 
persistent  white  line  in  the  skin  follows  the  drawing  of  the  finger 
nail  over  the  skin.  This  white  line  disappears  during  treatment. 
A  solution  of  adrenalin  chlorid  (1:1000)  may  be  given  well 
diluted  by  mouth  in  doses  of  20  drops  three  times  daily,  or  by 
rectum  in  double  this  amount  in  the  nutrient  enemata.  In  severe 
cases  hypodermics  of  .from  5  to  10  minims  are  indicated.  The 
most  recent  report  is  by  Rathery  and  Bordet,  who  arrested  at 
once  a  serious  vomiting  by  the  injection  of  250  cubic  centimeters 
of  normal  salt  solution  containing  10  drops  of  "epinephrin," 
repeated  daily  up  to  a  total  of  2.5  milligrams.  The  procedure  is 
worthy  of  further  trial. 

Nasopharyngeal  Complications. — The  association  between  the 
genitals  and  the  nasal  and  pharyngeal  mucous  membranes,  as 
manifested'  by  congestion  of  the  latter  during  the  menstrual 
period  and  the  reported  relief  of  dysmenorrhea  by  applications 
of  cocain  to  certain  areas  in  the  nose,  has  directed  attention  to  the 
possible  effect  on  hyperemesis  of  similar  procedures.  Nausea  and 
retching  on  rising  in  the  morning  provoked  by  a  nasopharyngeal 
catarrh  with  the  presence  of  tenacious  mucus,  must  be  treated  by 
alkaline  gargles  and  the  application  of  a  5  or  10  per  cent  solution 
of  nitrate  of  silver  to  the  affected  area.  If  examination  of  the 
nasal  passages  shows  a  red,  congested  turbinate  region,  local 
applications  of  a  2  per  cent  cocain  muriate  solution  or  adrenalin 
(i  :iooo)  often  give  remarkably  good  results. 

Sedative  Drugs. — The  use  of  sedative  drugs  in  hyperemesis 
has  been  largely  recommended  by  those  who  insist  that  a 
"nervous  habit"  accounts  for  many  cases  of  moderate  severity, 
and  that  the  act  of  vomiting  is  simply  a  response  to  the  feeling  of 
nausea.  In  addition  to  dietetic  regulations  and  a  sojourn  in  a 
hospital,  Lynch,  for  example,  advises 'keeping  the  patient  under 
the  constant  influence  of  large  doses  of  bromid  by  rectum,  begin- 
ning with  doses  of  from  40  to  60  grains  every  four  hours,  and  con- 
tinuing until  cessation  of  the  vomiting. 

OPIUM. — The  rectal  administration  of  powdered  opium  in  sup- 
positories of  from  i  to  2  grains  at  four-hour  intervals,  has  occa- 


io8  TOXEMIAS  OF   PREGNANCY 

sionally  given  me  good  results,  also  in  asthenic,  tired-out  women, 
the  hypodermic  use  of  l/%  grain  of  morphin  every  three  or  four 
hours,  or  i  grain  of  codein  at  similar  intervals.  The  employment  of 
other  narcotics  and  hypnotics,  including  trional,  sulphonal,  etc.,  has  not 
been  satisfactory.  But  a  period  of  rest  secured  by  opiates  often 
tides  the  patient  over  a  time  during  which  eliminatory  and  feed- 
ing measures  may  help  to  restore  a  balance. 

IPECAC. — It  is  usually  assumed  that  excessive  vomiting  nroduces 
a  condition  of  the  mucous  membrane  of  the  stomach  akin  to  gas- 
tritis, that  is,  one  of  extreme  congestion.  This  is  probably  true, 
but 'if  there  is  marked  nausea  without  much  vomiting,  the  circula- 
tion of  the  stomach  is  likely  to  be  poor  and  its  activity  depressed. 
In  this  condition  ipecac  has  been  shown  to  be  of  value,  drop  doses 
of  the  wine  in  a  teaspoonful  of  water  at  half-hour  intervals  having 
been  found  very  efficient.  Care  must  be  taken  to  exclude  cases  of 
actual  gastritis,  as  the  nausea  or  vomiting  from  the  latter  will  be 
rendered  worse  by  this  drug. 

COCAIN,  MENTHOL,  ETC. — The  administration  of  cocain,  menthol, 
peppermint,  and  similar  preparations  for  their  sedative  effect  on 
the  gastric  mucosa  has  not  given  me  any  good  results,  nor  has 
the  use  of  pure  carbolic  in  minim  doses  well  diluted.  Cocain 
muriate  in  doses  of  ^  grain  with  a  small  quantity  of  water  given 
before  eating  will  occasionally  favor  the  retention  of  food,  but  its 
effects  are  very  uncertain.  The  subcarbonate  of  bismuth  in  10- 
grain  doses  given  in  water  seems  to  have  a  better  effect. 

Blood  Transfusion. — The  indications  for  the  injection  of 
human  blood  have  also  been  extended  to  include  the  toxemias  of 
pregnancy,  both  in  the  early  and  late  months.  Thus,  Keator 
reports  a  case  in  which  severe  hyperemesis  in  the  third  month  of 
pregnancy  was  associated  with  purpuric  skin  areas,  nose  bleed, 
and  jaundice.  The  condition  did  not  respond  to  treatment  and 
the  uterus  was  emptied.  Hemorrhages  from  various  places  con- 
tinued, however,  and  the  clotting  time  of  the  blood  was  over  ten 
minutes.  The  undoubted  hemophilia,  although  no  previous  his- 
tory of  earlier  attacks  was  obtainable,  prompted  blood  transfusion 
by  the  direct  artery  to  vein  method.  Collapse  resulted,  but  the 
patient  finally  made  a  good  recovery.  The  occasional  appearance 
of  purpuric  spots  and  mucous  membrane  hemorrhages  in  severe 
cases  of  hyperemesis  furnishes,  it  seems  to  me,  a  good  indication 
for  blood  transfusion. 


TREATMENT  109 


ACUTE  YELLOW  ATROPHY  OF  LIVER 

Unfortunately  little  can  be  said  of  the  treatment  of  acute  yellow 
atrophy  of  the  liver.  As  soon  as  the  diagnosis  has  been  determined, 
immediate  emptying  of  the  uterus  is  indicated,  although  some  success- 
ful case  reports  are  on  hand  in  which  temporizing  measures  were 
resorted  to.  The  operation  must  be  performed  with  a  minimum  of 
shock,  as  already  described,  and  the  after-care  of  the  case  requires  the 
utmost  skill  and  patience.  The  prognosis  is  unfortunately  so  bad  that 
nothing  can  be  done  in  the  majority  of  these  cases. 


NEPHRITIS  AND  ECLAMPSIA 

The  treatment  of  nephritic  and  preeclamptic  toxemia  need  not 
be  discussed  separately  but  can  be  considered  with  that  of  eclamp- 
sia. The  appearance  in  pregnancy  of  the  symptoms  noted  in  a 
previous  chapter  under  this  head  should  always  call  for  prophy- 
lactic measures.  If  the  diagnosis  of  a  preeclamptic  condition  has 
been  made,  careful  and  frequently  repeated  urinalyses  are  essen- 
tial and  the  amount  of  albumin  should  be  carefully  watched  by 
means  of  an  Esbach  tube.  The  ordinary  boiling  and  ring  tests 
are  insufficient.  When  from  ^  to  I  gram  of  albumin  per  liter  is 
present,  the  diet  should  at  once  be  restricted  to  milk,  cereals  and 
toast,  with  as  much  water  as  possible.  The  patient  should 
be  put  to  bed  and  kept  quiet.  The  so-called  "imperial  drink" 
(cream  of  tartar,  I  teaspoonful,  juice  of  half  a  lemon,  water, 
I  pint,  with  sugar  to  flavor)  is  a  very  agreeable  beverage  and 
also  slightly  diuretic.  At  least  thirty  to  forty  ounces  of  urine 
should  be  passed  by  the  patient  every  twenty-four  hours.  The 
skin  must  be  kept  functionating  with  daily  warm  baths,  and  a 
saline  purge  (magnesium  sulphate)  at  regular  intervals  is  neces- 
sary. 

The  blood-pressure  should  be  carefully  watched  and  if  it  persists 
between  180  to  200,  palliative  treatment  should  be  supplemented  by 
more  radical  measures,  especially  if  the  albuminuria  goes  up  to  5  grams 
or  more  per  liter.  Hot  packs,  arterial  dilators  (chloral  in  doses  of 
from  5  to  10  grains  every  four  hours)  and  colonic  irrigations  may 
again  be  tried,  but  preparations  for  the  induction  of  labor  should 


no  TOXEMIAS  OF  PREGNANCY 

always  be  made.  The  abstraction  of  a  pint  or  more  of  blood  in  other- 
wise vigorous  and  well-nourished  patients  may  be  resorted  to,  but  I 
am  not  inclined  to  favor  this  procedure  because,  whatever  method 
of  delivery  is  finally  employed,  may  result  in  such  considerable 
blood  loss  that  marked  shock  results.  If  a  woman's  condition  is 
so  serious  as  to  require  venesection,  it  is  usually  grave  enough  to 
call  for  the  emptying  of  the  uterus. 

Eclampsia,  Treatment  of. — In  beginning  the  discussion  of  the 
treatment  of  the  final  group  in.  our  classification,  it  may  be  noted 
that  during  the  last  quarter  of  a  century  the  treatment  of  eclamp- 
sia, using  this  term  in  its  broader  sense,  has  vacillated  between 
two  extreme  views  and  even  at  the  present  time  there  are  many 
adherents  in  each  camp,  although  the  number  of  those  who  favor 
a  middle  ground  is  constantly  increasing.  During  the  period  when 
the  eclamptic  woman  was  supposed  to  be  suffering  from  a  func- 
tional kidney  disorder  and  immediate  relief  was  believed  to  con- 
sist in  bleeding,  a  great  deal  of  harm  was  done  because  the  cases 
were  not  selected.  Stout  women  bore  bleeding  well  and  often 
recovered,  but  the  thin,  frail  type  usually  succumbed  or  under- 
went a  prolonged  convalescence.  After  it  was  recognized  that 
the  fetus  itself  might  be  the  exciting  cause  of  the  symptoms, 
immediate  emptying  the  uterus  was  advocated  and  the  forcible 
dilatation  of  the  cerxix  uteri  with  mechanical  dilators,  such  as  the 
Bossi,  was  widely  practiced.  As  the  result  of  these  methods  of 
accouchement  force,  the  lower  genital  tract  was  subjected  usually  to 
extensive  lacerations  writh  excessive  shock,  loss  of  blood,  and  frequent 
sepsis,  together  with  more  or  less  permanent  mutilation  of  the  parts. 

It  was  soon  admitted  that  such  methods  were  contrary  to  the  best 
interests  of  the  patient,  and,  where  the  idea  of  immediate  delivery 
still  persisted,  more  skillful  methods  were  called  into  play,  including 
the  Diihrseen  incisions,  the  vaginal  cesarean  section,  and  later  the 
abdominal  variety  of  this  operation.  At  the  same  time  we  find 
Stroganoff  and  his  adherents  endeavoring  to  enforce  their  ideas,  based 
on  very  conservative  methods,  in  which  little  attention  was  paid  to  the 
fetus  in  utero,  but  every  means  was  taken  to  reduce  the  process  of 
toxin  formation  in  the  mother  and  to  overcome  its  irritating 
effects  by  the  administration  of  morphin  and  other  sedative  drugs. 

Besides  the  conservative  Stroganoff  procedure,  venesection 
and  methods  of  delivery  characterized  by  less  radical  procedures, 
such  as  the  introduction  of  bougies,  vaginal  packs  and  the  dilating 


TREATMENT  in 

bags,  are  now  more  widely  employed,  but  we  are  still  unfor- 
tunately groping  for  a  method  of  treatment  that  will  meet  more 
specific  indications.  In  the  present  state  of  our  knowledge,  how- 
ever, it  is  just  as  well  that  we  refrain  from  innovations  in  treat- 
ment, and  select  those  procedures  in  which  experience  has  shown 
the  lowest  possible  mortality,  both  for  the  mother  and  child,  and 
a  minimum  of  subsequent  injury  to  the  mother.  In  view  of  our 
ignorance  of  the  etiology  of  eclampsia  it  would  be  unfair  to 
recommend  any  one  method  of  treatment.  Each  individual  case 
should  be  thoroughly  studied  and  the  procedures  selected  which 
are  best  adapted  to  the  surroundings  of  the  patient  on  the  one 
hand,  and  the  skill  of  the  attendant  on  the  other.  This  seems 
much  more  sensible  than  to  claim  that  all  cases  coming  under 
observation  must  be  handled  according  to  a  routine  procedure. 
In  other  words,  as  I  have  repeatedly  stated,  the  patient,  and  not 
the  disease,  is  to  be  treated. 

PROPHYLACTIC  MEASURES. — The  simplest  conception  of  the  treat- 
ment of  this  disturbance  includes  first,  the  management  of  the 
so-called  preeclamptic  stage;  second,  that  of  the  series  of  phenom- 
ena to  which  the  term  "true  eclampsia"  is  usually  applied.  Be- 
fore proceeding,  however,  to  the  discussion  of  the  manner  of 
dealing  with  the  preeclamptic  stage,  described  in  a  general 
way  in  the  preceding  section,  we  must  take  into  consideration  the 
prophylactic  handling  of  these  patients,  as  soon  as  any  warnings 
of  a  disturbance  in  the  body  metabolism  become  evident.  It  is 
generally  assumed  that,  under  ordinary  circumstances,  in  a  preg- 
nant woman  in  good  general  health,  with  emunctories  in  working 
order,  no  particular  danger  from  this  source  exists.  It  is  unwise, 
however,  to  agree  with  this  complete  optimism.  Pregnant 
women,  even  if  apparently  well,  should  be  looked  upon  as  being 
in  an  extremely  unstable  condition  in  regard  to  their  metabolism 
and  subject  to  very  sudden  deviations  in  the  normal  bodily  func- 
tions. It  is  therefore  advisable  for  the  attending  physician  in 
every  case  of  pregnancy  to  warn  the  patient  of  what  may  occur 
in  the  way  of  symptoms  that  in  time  might  lead  to  an  eclamptic 
seizure. 

Preventive  measures  in  the  preeclamptic  stage  are  simply 
those  recognized  as  essential  in  the  ordinary  hygiene  of  preg- 
nancy, that  is,  good  food,  plenty  of  fresh  air,  moderate  exercise, 
attention  to  the  emunctories,  peace  of  mind  and  freedom  from 


U2  TOXEMIAS  OF  PREGNANCY 

care  and  worry.  When  these  can  be  provided  a  great  part  of  the 
battle  against  abnormal  deviations  is  already  won.  It  is  not  neces- 
sary to  pursue  this  phase  of  the  subject  further,  as  it  has  been 
amply  treated  elsewhere.  It  is  well,  however,  to  mention  here 
the  deviations  from  the  normal  upon  which  to  base  our  estimate 
as  to  whether  the  patient's  physiology  is  fulfilling  the  calls  made 
upon  it.  First  and  foremost,  every  pregnant  woman  should  be 
seen  at  regular  intervals  by  her  chosen  attending  physician,  at 
which  times  she  must  bring  a  part  of  the  twenty-four-hour  urine 
specimen  for  examination.  Patients  should  also  be  urged  to  note 
any  unusual  occurrences  during  the  interval  since  the  last  visit 
and  be  ready  to  consult  their  physician  with  reference  to  the 
same.  The  visits  should  be  made  at  no  greater  than  monthly 
intervals  and  if  abnormalities  are  present  more  frequent  visits  are 
necessary. 

The  patient  should  be  carefully  questioned  at  the  office  visit 
about  the  condition  of  her  bowels,  frequency  of  urination,  head- 
aches, digestive  disturbances,  pain,  visual  abnormalities,  etc.  Not 
every  patient  presenting  deviations  from  the  normal  in  the 
symptoms  referred  to  is  necessarily  in  the  preeclamptic  stage. 
Headaches  may  be  due  to  other  causes,  and  if  unassociated  with 
albuminuria  or  other  urinary  abnormalities,  edema,  or  visual  dis- 
turbances, they  may  be  treated  in  the  accepted  manner.  The  intes- 
tinal tract  is  at  fault  in  a  great  many  cases  as  well  as  the  eyes; 
and  if  headaches  persist,  notwithstanding  attention  to  the  cor- 
rection of  digestive  disturbances,  and  if  accompanied  with 
irregular  vision,  it  is  advisable  to  have  the  patient  consult  an 
ophthalmologist.  The  correction  of  visual  disturbances,  which 
may  not  have  been  present  before  pregnancy,  or  at  least  not  in  an 
annoying  form,  should  be  urged  upon  the  patient,  and  in  a  great 
many  instances  it  will  be  found  that  the  wearing  of  glasses 
relieves  headaches  that  were  considered  a  symptom  of  the  pre- 
eclamptic stage. 

Although  we  accept  pain  in  the  pit  of  the  stomach  as  a  fore- 
warning of  an  eclamptic  seizure,  this  is  not  true  in  every  case. 
Hyperacidity  is  a  frequent  accompaniment  of  pregnancy,  and  in 
some  cases  the  resulting  distress  after  eating  is  not  only  annoying 
but  may  alarm  the  patient  and  also  her  attending  physician.  If 
present,  as  it  so  frequently  is  during  the  later  months  of  preg- 
nancy, it  should  be  alleviated  by  the  administration  cu  alkalis, 


TREATMENT  1 13 

such  as  soda  bicarbonate,  milk  of  magnesia,  aromatic  spirits  of 
ammonia,  etc.  I  have  had  good  results  from  dilute  hydrochloric 
acid  in  ten-drop  doses  three  times  daily  after  meals.  Patients 
who  are  afflicted  with  indigestion  and  take  large  amounts  of 
bicarbonate  of  soda  for  relief  often  suffer  general  abdominal 
cramplike  pains  which  cease  when  the  drug  is  stopped.  It  is  not 
advisable  to  continue  any  one  alkali  for  a  prolonged  period. 

Constipation. — The  constipation  which  is  such  a  frequent  and 
annoying  symptom  in  the  latter  months  of  pregnancy  must  be 
combated  in  every  case,  because  we  may  safely  assume  that  it  is 
an  underlying  factor  in  the  production  of  many  toxemias.  Advice 
on  the  relief  of  constipation  has  taken  so  many  turns  that  it  would 
be  a  difficult  matter  to  present  it  in  its  entirety.  The  regulation 
of  the  diet,  however,  so  as  to  include  a  minimum  of  meat,  soup, 
cocoa,  tea,  white  bread  and  similar  articles,  is  essential  no  matter 
what  form  of  drug  catharsis  is  employed.  The  response  to  treat- 
ment varies  with  the  individual,  but  in  any  case  purging  is  contra- 
indicated.  The  regular  administration  of  fluid  extract  of  cascara 
in  doses  of  from  15  to  30  minims  with  I  or  2  drachms  of  rhubarb 
and  soda  mixture  is  usually  effective.  The  stronger  vegetable 
cathartic  pills  should  be  avoided,  especially  those  containing  an 
admixture  of  aloes.  The  use  of  heavy  mineral  oils  has  been 
widely  advocated,  but  the  response  depends  on  the  individual 
patient.  In  some  cases  the  administration  of  an  ounce  or  two  of 
petroleum  oil  at  bedtime,  together  with  a  mild  cathartic,  has 
proved  very  efficacious,  but  in  others  absolutely  no  result  is 
obtained.  The  oil,  to  be  efficient,  must  be  taken  over  a  long 
period  and  is  rarely  effective  unless  combined  with  a  cathartic. 

Phenolphthalein  has  also  been  recommended  as  an  ideal  lax- 
ative in  pregnancy.  Its  use,  however,  cannot  be  long  continued, 
because  of  its  irritating  effect  on  the  kidneys.  While  frequent 
water  drinking  has  a  good  effect  in  favoring  bowel  action,  the 
hard  water  from  commonly  found  artesian  well  supply  is  pro- 
ductive of  an  opposite  effect.  When  the  water  is  known  to  be 
hard  it  should  be  boiled  before  use  and  thoroughly  aerated. 
Resort  to  enemas  may  be  necessary  and  I  have  rarely  seen  any 
bad  effects  from  them  in  women  who  had  a  great  deal  of  diffi- 
culty in  securing  proper  bowel  action,  even  with  the  assistance  of 
cathartics.  Given  in  the  form  of  a  pint  of  hot  soap  suds  with  the 
patient  lying  on  her  left  side  and  repeated  if  the  first  injection  is 


n4  TOXEMIAS  OF  PREGNANCY 

ineffective,   enemas   need   not,   in   my   opinion,   become   a   habit- 
forming  procedure. 

Organs  of  Elimination,  Care  of. — The  necessity  of  maintaining 
proper  excretion  through  the  medium  of  the  skin  and  kidneys  is 
obvious  and  can  best  be  secured  by  the  free  drinking  of  water  and 
by  bathing.  A  warm  bath  every  day  or  two  in  the  evening  on 
retiring  is  indicated  during  pregnancy,  but  I  do  not  approve  of 
the  cold  showers  on  arising  in  which  some  women  indulge.  I 
believe  that  the  chilling  of  the  body  which  results  is  unfavorable 
and  may  even  be  a  source  of  danger.  However,  those  patients 
who  have  become  accustomed  to  cold  showers  may  resent  their 
prohibition  at  this  time,  but  they  should  be  warned  against  them. 

The  amount  of  urine  excreted  during  twenty-four  hours  should 
reach  at  least  two  or  three  pints  and  I  often  direct  patients  actually 
to  measure  the  urine  once  a  week,  noting  at  the  same  time  the 
color  and  odor.  I  consider  a  reduction  in  the  quantity  of  urine 
with  an  increase  in  the  specific  gravity  a  sign  always  to  be  taken 
note  of.  Patients  are  very  apt  to  drink  freely  of  water  the  day 
before  coming  to  the  doctor's  office  so  as  to  be  provided  with  a 
proper  specimen.  They  should  therefore  be  instructed  that  nor- 
mal urinary  conditions  must  be  insisted  upon  at  all  times. 

These  more  or  less  simple  prophylactic  measures  may  be  suf- 
ficient in  most  cases  to  preserve  the  woman's  normal  metabolism 
under  ordinary  circumstances.  There  is  a  certain  group  of  cases, 
however,  in  which  mild  toxic  states  are  present,  characterized  by 
frontal  headache,  torpor,  reduction  in  urinary  output,  etc.,  that 
calls  for  somewhat  more  vigorous  treatment.  A  patient  who  pre- 
sents herself  with  this  train  of  symptoms  must  be  cautioned 
against  the  gravity  of  her  condition,  without,  of  course,  frighten- 
ing her.  It  is  better  to  err  on  the  safe  side  even  if  the  restrictions 
imposed  on  the  patient  seem  onerous.  The  protein  foods  in  such 
cases  should  be  immediately  reduced  and  a  diet  of  milk  and  cereals 
prescribed,  together  with  mild  catharsis  until  improvement 
results. 

The  ordinary  examination  of  the  urine  may  not  show  any- 
thing more  than  a  mere  trace  of  albumin  and  perhaps  increased 
specific  gravity,  but  tests  for  indican  and  diacetic  acid  should 
always  be  made.  The  so-called  clearing-out  process  in  such 
patients  must  not,  however,  be  overdone.  The  administration  of 
large  doses  of  calomel  and  salts  is  not  necessary.  In  fact,  calomel 


TREATMENT  115 

and  salts  should  not  be  given  to  the  delicate  type  of  woman,  but 
reserved  rather  for  those  who  are  well-nourished,  who  present  a 
florid  complexion,  and  who  are  inclined  to  stoutness.  In  the 
latter  2  grains  of  calomel  in  divided  doses  during  the  afternoon 
are  to  be  followed  by  a  tablespoonful  of  Epsom  or  similar  salts  in 
hot  water  the  next  morning  and  an  enema  a  few  hours  later.  This 
dose  may  be  repeated  at  intervals  of  from  five  to  ten  days;  other- 
wise, somewhat  larger  doses  of  cascara  than  the  patient  has 
been  accustomed  to,  or  small  doses  of  castor  oil  (*/j  ounce  at  bed- 
time), are  valuable.  As  a  general  rule,  the  symptoms  will  subside 
under  these  restrictions,  but  a  patient  should  be  instructed  to 
report  at  once  to  her  physician  if  no  improvement  results,  or  if 
the  symptoms  become  worse. 

Blood-pressure.  —  Blood-pressure  observations  should,  of 
course,  be  taken,  but  in  many  cases  we  do  not  find  any  rise  of 
blood-pressure  associated  with  the  group  of  cases  described  in  the 
preceding  paragraph.  The  subject  of  blood-pressure  observations 
and  their  significance  has  already  been  referred  to  in  another 
chapter.  The  apparatus  for  such  observations  gives  very  trust- 
worthy information,  but  it  must  be  used  intelligently  and  with 
due  consideration  to  the  patient.  Small,  asthenic,  poorly  nour- 
ished individuals  may  show  low  blood-pressure,  although  suffer- 
ing from  moderate  degrees  of  toxemia;  whereas  the  stout,  well- 
nourished  patient  with  a  high  blood-pressure  may  so  mislead  the 
physician  that  he  believes  an  eclamptic  seizure  imminent.  Such 
observations  must  always  be  taken  into  consideration  with  the 
urinary  findings  and  the  other  symptoms.  Women  who  present 
moderate  and  continuous  elevations  of  blood-pressure  in  associa- 
tion with  the  train  of  symptoms  already  referred  to  may  be  given 
arterial  dilators  if  the  dietetic  and  cathartic  measures  do  not  pro- 
duce a  result.  For  instance,  a  full-blooded  patient  in  her  third 
or  fourth  pregnancy,  who  is  running  a  diastolic  pressure  of  150 
millimeters  or  more,  who  complains  of  congestive  headaches,  and 
who  has  a  flushed  appearance  and  a  full  pulse,  may  take  chloral 
hydrate  in  5-grain  doses  three  or  four  times  daily  with  advantage 
for  periods  of  four  or  five  days,  combined  with  rest  in  bed.  Relief 
from  headache  and  nervousness  is  usually  noted  within  a  day  or 
so.  As  soon  as  the  blood-pressure  falls  twenty  points  or  more  the 
administration  of  the  drug  should  cease. 

The  use  of  nitroglycerin  in  stout  patients  with  high  blood- 


n6  TOXEMIAS  OF  PREGNANCY 

pressure  has  not  been  effective  in  my  experience.  Unless  we 
can  give  nitroglycerin  in  comparatively  large  doses  and  know 
that  the  preparation  is  fresh,  or  unless  we  can  use  the  spiritus 
glonoin,  the  administration  of  this  arterial  dilator  is  of  no  value. 
Moreover,  the  mouth  administration  of  the  drug  is  practically 
without  result,  and  I  have  had  results  only  if  administered  hypo- 
dermically.  There  is  no  indication  whatever  for  giving  veratrum 
viride  at  this  time.  Rest  in  bed  is  a  very  important  factor  in  the 
more  rapid  recovery  of  these  patients,  and  it  may  be  necessary  in 
some  instances  to  remove  them  from  unsatisfactory  surroundings 
to  a  hospital,  where  improvement  in  their  condition  is  usually 
noted  immediately. 

Visual  Disturbances. — Patients  who  present  the  train  of  symp- 
toms which  includes  headache,  malaise,  digestive  disturbances,  coated 
tongue,  and  occasional  attacks  of  dizziness,  must  be  kept  under 
the  most  careful  observation,  for  at  any  moment  the  picture  may 
grow  suddenly  worse.  In  most  instances,  however,  sufficient 
warning  is  given  through  the  medium  of  the  visual  apparatus, 
and  should  be  heeded  immediately.  The  attending  physician 
should  always  take  note  of  photophobia,  diplopia  and  other  ocular 
abnormalities,  for  their  appearance  demands  the  most  careful 
attention.  Keeping  the  patient  in  a  darkened  room  is  very  helpful 
in  reducing  the  irritability  of  the  eyes.  It  is  advisable  whenever 
possible  to  have  an  examination  of  the  eye-grounds  made  by  an 
ophthalmologist.  The  latter  can  detect  retinal  changes  in  which 
more  vigorous  action  may  be  indicated.  As  I  have  already  stated 
in  the  description  of  the  pathology  of  eclampsia,  the  eye  symptoms 
associated  with  this  condition  may  prove  extremely  serious.  The 
presence  of  retinal  hemorrhages  or  the  picture  designated  as  albu- 
minuric  retinitis,  even  if  not  associated  with  transitory  or  per- 
manent blindness,  always,  in  my  opinion,  calls  for  the  emptying  of 
the  uterus.  I  do  not  believe  that  a  policy  of  hesitancy  should  pre- 
vail in  these  cases  in  view  of  the  known  fact  that  permanent 
damage  to  the  eyes  may  result,  even  if  the  acute  toxic  condition 
ends  in  recovery,  and  that  more  serious  intracranial  lesions  may 
be  in  process  of  development. 

Convulsions. — In  another  group  of  cases  in  which  the  presence 
of  convulsions  is  the  distinguishing  characteristic,  opinions  differ 
widely  as  to  the  proper  treatment.  For  many  years  the  pendulum 
has  swung  from  extreme  conservatism  to  extreme  radicalism  and 


TREATMENT  117 

back  again,  and  at  the  present  time  there  is  by  no  means  accord 
as  to  the  proper  procedure.  It  seems  to  me  that  here,  as  under 
other  circumstances,  recourse  to  a  middle  ground  is  most  essen- 
tial, and  the  careful  study  of  the  individual  patient  should  be  the 
guiding  feature  rather  than  adherence  to  any  routine  method  of 
procedure.  It  may  be  granted  that  in  a  given  case  the  doing 
away  with  the  convulsions  is  the  essential  feature  in  the  treat- 
ment. Assuming  that  the  muscular  spasms  are  due  to  cortical 
irritation,  they  may  be  most  satisfactorily  subdued  by  the 
administration  of  sedative  drugs,  which  has  found  expression  in 
the  extensive  employment  of  the  so-called  Stroganoff  method, 
which  treats  only  this  symptom,  and  after  the  patient  is 
narcotized  the  natural  termination  of  the  labor  is  awaited.  Its 
advocates  bring  forward  a  large  series  of  cases  thus  treated  with 
exceedingly  good  results.  It  must  be  admitted,  however,  that  the 
emptying  of  the  uterus  is  often  followed  by  a  cessation  of  the  convul- 
sions and  an  improvement  of  the  patient  in  most  cases.  For  this  reason 
it  would  appear  better  as  a  general  procedure  to  adopt  the  favor- 
able features  of  both  methods  of  treatment. 

Perhaps  the  description  of  the  treatment  of  an  ordinary  case  of 
eclamptic  convulsions  will  explain  this  more  satisfactorily.  What  shall 
be  done  in  a  given  case  in  which  the  physician  finds  that  the  patient  has 
had  one  or  more  general  convulsive  seizures  with  a  typical  clinical 
picture  that  leads  to  the  diagnosis  of  a  true  eclampsia?  First  and  fore- 
most, the  decision  should  be  made  to  refer  the  patient  to  a  hospital 
whenever  possible,  but  in  the  meantime  it  is  necessary  to  reduce  the 
possibility  of  further  convulsions  and  this  can  be  most  simply  and  satis- 
factorily secured  by  the  proper  administration  of  opium.  Thus  ^4  of  a 
grain  of  morphin  sulphate  with  1/150  of  atropin  sulphate  may  be  given 
by  hypodermic  immediately,  to  be  repeated  at  intervals  of  one,  two,  or 
three  hours,  depending  on  the  severity  of  the  seizure.  Meanwhile 
preparations  can  be  made  for  the  transfer  of  the  patient.  No  one 
need  hesitate  to  administer  morphin  in  such  cases  until  the  full 
and  complete  physiological  result  is  secured,  as  evidenced  by  the 
fall  of  the  respirations  to  sixteen  or  even  to  fourteen  per  minute. 
Atropin  may  b'e  objected  to  as  an  accompaniment  because  of  its 
well  known  desiccating  effect  on  the  secretions,  but  its  value  in 
overcoming  certain  undesirable  effects  of  the  opium  more  than 
compensates  for  any  possible  physiological  effect  of  its  own. 
Moreover,  atropin  is  a  relaxant  of  muscular  tissue,  especially  of 


uS  TOXEMIAS   OF   PREGNANCY 

the  unstriped  variety  and  reduces  the  tendency  to  pulmonary 
edema. 

Examinations,  Vaginal  and  Rectal. — No  attempt  should  be 
made  to  examine  a  patient  in  eclampsia  until  she  has  become 
thoroughly  narcotized,  because  such  an  examination  may  be  suf- 
ficient to  set  up  further  convulsive  spasms.  Chloroform  should 
never  be  employed  to  secure  the  necessary  relaxation,  but  ether 
may  be  used  with  less  danger.  The  tongue  must  be  protected 
against  injury  by  inserting  a  wedge  of  wood  (a  clothespin,  the 
handle  of  a  hairbrush,  or  a  spoon)  between  the  molar  teeth,  to  be 
retained  in  place  during  the  convulsive  seizure  and  reinserted  as 
needed.  I  would  suggest  omitting  the  vaginal  examination  in 
such  patients  unless  the  vulva  can  be  shaved  and  properly 
cleansed  because  we  know  that  the  resistance  to  general  infection 
in  these  women  is  very  greatly  lowered.  A  rectal  examination  is 
perhaps  preferable  at  this  time.  If  it  is  found  that  the  cervix  is 
dilated  three  ringers  or  more,  the  membranes  may  be  ruptured 
and  this  relief  from  intra-abdominal  tension  often  has  a  favorable 
effect  in  stopping  the  convulsions. 

Enemas  and  Stomach  Washing. — By  this  time  the  family  of  the 
patient  should  have  arrived  at  a  decision  as  to  the  transfer  to  a 
hospital,  and  where  this  is  possible  the  further  steps  in  the  treat- 
ment can  be  continued  in  the  institution.  It  may  be  necessary, 
however,  to  carry  out  further  treatment  at  home.  The  bowels 
should  be  washed  out  with  an  enema  of  hot  soap  suds  as  soon  as 
the  morphin  has  become  effective.  It  is  advisable  to  wash  the 
stomach,  but  unless  a  stomach  tube  can  be  skillfully  introduced  it 
is  better  to  omit  this  procedure,  as  the  introduction  may  induce 
further  convulsions,  or  the  accidental  inspiration  of  vomited 
material  may  result  in  later  pulmonary  complications.  If  the 
patient  should  become  even  moderately  conscious  after  the  con- 
vulsion, as  they  frequently  do,  water  can  be  freely  administered 
by  mouth  or  by  the  rectum  after  the  bowel  has  been  emptied  by 
an  enema. 

Induction  of  Labor. — It  is  not  advisable  to  make  any  efforts 
at  delivery  unless,  for  example,  the  head  should  be  near  enough 
to  the  outlet  to  permit  of  an  easy  forceps  extraction,  or  unless,  as 
in  the  case  of  a  breech  presentation,  an  extraction  can  be  per- 
formed. The  introduction  of  a  bag  in  cases  where  the  cervical 
dilatation  has  not  progressed,  or  is  not  progressing  satisfactorily, 


TREATMENT  119 

may  always  be  considered,  although  it  should  be  limited  to  cases 
where  the  softening  is  well  advanced  and  the  bag  can  be  inserted 
without  previous  instrumental  dilatation.  The  modified  Cham- 
petier  de  Ribes  bag,  or,  as  it  is  popularly  known  in  this  country, 
the  Voorhees  bag,  is  the  best  for  the  purpose.  The  digital  method 
of  dilating  the  cervix  is  tedious  and  time-consuming  and  lacera- 
tions are  certain  to  result.  The  Bossi  dilator  and  similar  instru- 
ments are  merely  mentioned  to  be  condemned. 

Delivery. — With  the  rupture  of  the  membranes,  either  spon- 
taneously or  artificially,  labor  comes  on  in  many  cases  and  may 
be  allowed  to  proceed  even  while  the  other  details  of  the  treat- 
ment are  being  carried  out.  Hot  packs  seem  to  have  a  stimulating 
effect  on  labor  pains  and  the  baby,  particularly  if  premature,  is 
sometimes  born  in  the  blankets.  Occasionally  in  a  multipara  with 
a  soft,  dilated,  or  dilatable  cervix,  and  no  engagement  of  the  pre- 
senting part,  version  can  be  performed  with  advantage  under 
ether  anesthesia.  In  primiparae,  however,  in  whom  no  evidences 
of  labor  are  present,  the  attempt  to  induce  labor  when  the  cervix 
is  not  dilated  is  unjustifiable.  It  is  better  to  continue  the  general 
sedative  and  eliminant  treatment  of  these  patients  rather  than 
resort  to  accouchement  force  with  its  necessary  mutilations  to  the 
mother  and  possible  death  to  the  child.  Conservation  of  the 
patient's  strength  is  always  of  primary  importance,  and  no  pro- 
cedure should  be  resorted  to  that  would  in  any  way  reduce  her 
chances  of  recovery. 

Rectal  Infusions. — If  the  patient  is  brought  to  a  hospital  (and 
this  is  always  a  great  desideratum),  more  regular  and  efficient 
treatment  can  usually  be  instituted.  After  the  initial  enema  and 
stomach  washing,  fluid  should  be  given  by  rectum  at  regular  intervals. 
This  may  be  done  by  colonic  irrigations  or  by  simple  rectal  infusions  of 
eight  ounces  of  glucose  solution  (from  I  to  5  per  cent),  or  soda  bicar- 
bonate solution  (from  i/io  to  5  per  cent).  The  main  point  in  the 
irrigation  is  that  it  shall  be  sufficiently  large  in  volume — from  three  to 
four  gallons  at  a  time,  at  a  temperature  of  at  least  1 10°  F.  At  the  con- 
clusion of  the  irrigation  a  pint  of  the  solution  should  be  left  in  the 
rectum  and  the  patient  placed  in  a  hot  wet  or  dry  pack  if  her  physical 
condition  indicates  it.  The  presence  of  edema  in  a  well-nourished 
patient  should  be  taken  as  the  deciding  factor  and  I  do  not  believe 
that  small,  emaciated  women  with  low  blood-pressure  and  little 
subcutaneous  fat,  or  edema,  should  be  subjected  to  the  debili- 


I2O 


TOXEMIAS  OF  PREGNANCY 


tating  influence  of  a  sweat  pack.  The  irrigations  alone  are  suf- 
ficient for  them  and  natural  perspiration  may  be  awaited.  The 
hot  wet  packs  with  an  ice  bag  or  cold  towel  applied  to  the  head 
are  not  continued  for  more  than  twenty  minutes  and  should  be 
followed  by  a  hot  dry  blanket  in  which  the  patient  is  kept 
wrapped  for  an  hour. 

The  irrigations  and  packs  may  be  repeated  at  intervals  of  from 
eight  to  twelve  hours,  according  to  the  response,  and  if  in  the 
interim  convulsions  again  come  on,  free  recourse  to  morphin  may 
be  had.  This  drug  after  the  initial  doses  and  until  a  definite  effect 
is  secured,  may  be  kept  in  reserve  and  further  possible  seizures 


200, 


190 


160 


no 


delivery 

12.       5  am  '6, 


QQlll  c< 


12 


FIG.  26. — BLOOD-PRESSURE  CHART  FROM  A  PRE-ECLAMPTIC,  SHOWING  LITTLE  EFFECT 
FROM  VERATRUM  VIRIDE  (Bailey). 

avoided  by  the  administration  of  chloral  hydrate  and  sodium 
bromid  given  in  the  first  rectal  infusion  in  doses  of  40  grains  of 
the  chloral  with  one  or  two  drachms  of  sodium  bromid,  or  the 
official  mixture  of  triple  bromids.  Blood-pressure  observations 
during  the  first  period  often  give  a  clue  as  to  the  effect  of  treat- 
ment by  which  a  pressure  of  from  170  to  over  200  before  or  after 
a  seizure  is  sometimes  reduced  20  to  30  points  within  a  few  hours. 
No  effort  should  be  made  to  reduce  the  blood-pressure  beyond 
these  figures,  as  it  is  necessary  to  keep  up  a  full  supply  of  blood 
in  the  organs  of  elimination  and  the  skin.  For  this  reason  I  do 
not  advocate  the  use  of  veratrum  viride,  as  it  brings  about  a 
marked  and  rapid  reduction  often  accompanied  by  severe  depres- 
sion and  shock  (Figs.  26-29). 

Labor,  Desirability  of. — With  the  patient  in  the  hospital  a  dif- 
ferent view  may  be  taken  of  the  desirability  of  inducing  labor. 


TREATMENT  121 

If  one  is  a  convert  to  the  extreme  conservative  therapy,  no  further 
attention  need  be  paid  to  the  induction  of  labor,  for,  as  already 
stated,  pains  very  often  come  on  spontaneously.  On  the  other 
hand,  if  one  feels  that  the  emptying  of  the  uterus  may  lead  to  a 
more  definite  result,  a  suitable  method  of  delivery  may  be  selected 
which,  however,  should  always  be  characterized  by  a  minimum  of 
shock  and  manipulation.  This  at  once  rules  out  accouchement  force 
and  the  possible  instrumental  dilatation  of  the  cervix  advocated 
some  years  ago.  Where  the  patient  is  near  term,  the  presenting 
part  engaged,  the  cervix  soft,  thinned  out,  and  permitting  the 
introduction  of  a  bag,  this  can  be  inserted  after  the  membranes  are 
ruptured.  On  the  other  hand,  given  a  primipara  at  the  eighth  or 
ninth  month  of  her  pregnancy  with  a  rigid,  undilated,  thick  cervix, 
a  large  baby,  rigid  soft  parts  and  perhaps  a  slight  degree  of  pelvic 
contraction,  the  abdominal  cesarean  section  serves  an  excellent 
purpose,  and  if  it  can  be  properly  done  frequently  saves  the  lives 
of  both  mother  and  child.  Unfortunately  the  child  often  dies  in 
cases  where  there  have  been  many  convulsive  seizures,  so  even 
the  disappointment  of  extracting  a  dead  baby  must  not  be 
regarded  as  a  factor  in  the  possible  performance  of  the  operation, 
because  the  mother  is  certainly  subjected  to  much  less  mutilation 
and  perhaps  hemorrhage  than  in  a  forcible  vaginal  method  of 
delivery. 

Care  of  Patient  after  Labor. — Unfortunately,  emptying  of  the 
uterus  does  not  always  bring  about  a  cessation  of  the  convulsions 
and  they  may  be  followed  by  a  condition  of  deep  coma  last- 
ing several  hours  and  sometimes  days.  In  no  case  should  the 
eliminatory  treatment  of  the  patient  be  stopped  after  the  uterus 
is  emptied,  and  irrigations  with  or  without  packs  should  be  con- 
tinued at  intervals  of  from  eight  to  twelve  or  twenty-four  hours 
until  the  patient's  mind  is  entirely  clear,  the  blood-pressure  de- 
clines and  the  kidney  function  is  good.  The  drinking  of  water 
during  this  period  is  essential,  and  if  the  patient  can  be  roused  the 
administration  of  diluted  milk  and  cereal  gruels  is  indicated. 
Chloral  in  5-grain  doses  every  four  hours  in  capsule  is  a  safe 
routine  procedure  after  delivery  and  may  be  continued  for  several 
days  until  the  declining  blood-pressure  gives  evidence  of  satis- 
factory arterial  dilatation. 

Urine  Examinations. — Urine  examinations  must  be  made  at 
least  once  a  day,  care  being  taken  to  get  clean  specimens  so  that 


122  TOXEMIAS  OF  PREGNANCY 

the  admixture  of  lochial  discharges  will  not  confuse  the  findings. 
A  clean  specimen  may  be  secured  by  catheter;  or,  if  the  patient  is 
conscious,  by  holding  a  sterile  pus  basin  directly  under  the  urinary 
meatus.  The  quantity  of  urine  passed  must  be  carefully  noted, 
and  if  it  remains  much  below  1,000  cubic  centimeters  in  twenty- 
four  hours,  notwithstanding  the  irrigations  and  rectal  injections, 
urination  may  be  stimulated  by  a  hypodermoclysis  with  normal 
soda  bicarbonate  solution  (never  with  salt).  In  advanced  cases 
marked  by  shock  and  extreme  prostration  there  is  no  objection  to 
the  intravenous  injection  of  the  bicarbonate  of  soda  or  glucose 
solution  (5  to  10  per  cent).  Not  more  than  600  or  700  cubic 
centimeters  should  be  injected  intravenously  in  order  not  to  over- 
strain the  mechanism  of  the  heart. 

After-care. — The  after-care  of  eclampsia  patients  is  important. 
As  I  have  already  stated  they  must  be  freely  supplied  with  water 
and  also  with  nourishment.  The  best  form  of  nourishment  is 
milk  and  cereal  gruels  supplemented  by  fruit  juices  a  few  days 
later.  The  breast  secretion  in  eclamptics  appears  later  than  usual, 
and  this  is  not  unfavorable  because  nursing  by  the  baby  of  an 
eclamptic  mother  must  be  absolutely  interdicted  for  at  least  three 
days  after  delivery  or  until  no  further  symptoms  of  the  condition 
are  present.  Newborn  babies  who  nurse  eclamptic  mothers  have 
been  known  to  develop  eclamptic  seizures  as  a  result.  If  the 
breasts  should  become  full  before  the  three  days  have  elapsed 
after  delivery,  they  may  be  emptied  by  a  breast  pump  and  the 
milk  thrown  away.  The  condition  of  the  urine  in  eclamptic 
patients  improves  rapidly,  as  a  general  rule,  after  delivery,  but 
marked  traces  of  albumin  and  an  abundance  of  granular  and 
hyaline  casts  may  persist  for  many  days.  This  means  that  the 
careful  observation  of  the  patient  must  be  continued  and  rest  in 
bed  insisted  upon  until  all  evidences  of  renal  irritation  have  sub- 
sided. 

Complications,  Treatment  of. — The  treatment  of  the  complica- 
tions associated  with  eclamptic  convulsions  must  be  treated  as 
under  other  circumstances.  Hemiplegia  occurs  occasionally, 
for  which,  of  course,  little  more  can  be  done  than  the  treat- 
ment of  the  toxemia  itself.  The  eye  lesions,  including  blindness, 
must  be  referred  to  an  ophthalmologist.  Fortunately  the  visual 
disturbances  are  temporary  in  most  instances,  although  retinal 
hemorrhages  near  the  macula  lutea  may  be  productive  of  per- 


TREATMENT  123 

manent  damage.  The  traumatized  tongue  is  often  a  source  of 
considerable  annoyance  to  the  patient,  particularly  if  associated 
with  sordes.  As  the  patient  is  unable  to  cleanse  her  teeth  and 
mouth  during  the  early  days,  oral  hygiene  must  be  carried  out  by 
the  nurse,  and  the  plentiful  application  of  peroxide  of  hydrogen  in 
half-strength  applied  with  a  cotton  swab  is  very  comforting  and 
the  use  of  some  of  the  generally  accepted  mouth  washes  is  also 
indicated. 

Other  Plans  of  Treatment. — Having  outlined  the  general  plan 
of  treatment  for  toxemia  in  the  later  months  of  pregnancy  which 
I  have  found  most  efficient  and  practical,  I  will  consider  in  greater 
detail  some  of  the  many  procedures  advocated  by  others. 

The  two  radically  opposed  camps  so  far  as  the  treatment  of 
the  acute  manifestations  of  eclampsia  is  concerned  have,  during 
recent  years,  gradually  come  to  meet  on  a  common  ground  and 
less  is  heard  of  absolute  dependence  on  any  one  or  other  method 
of  procedure.  Stroganoff,  of  Petrograd,  is  probably  the  most 
widely  known  of  the  so-called  conservative  group,  but  even  before 
his  recommendations  for  treatment  with  mild  doses  of  narcotics, 
Veit  and  Winckel  both  published  their  results  of  the  treatment 
of  the  convulsions  with  larger,  even  massive,  quantities  of  opium 
and  chloral.  Veit  used  frequently  repeated  doses  of  0.03  gram, 
or  a  total  of  0.2  gram,  in  from  four  to  seven  hours.  In  a  series  of 
60  cases  reported  by  him  there  were  only  4  fatalities  (6  per  cent 
plus).  Subsequently  he  advised  in  severe  cases  the  use  of  warm 
baths  and  hot  blankets.  Veit  did  not  approve  of  venesection. 

Winckel  was  able  at  the  same  time  to  report  a  satisfactory 
method  of  controlling  eclamptic  convulsions  with  rectal  instilla- 
tions of  chloral  hydrate  in  doses  of  from  I  to  2  grams  (15  to  30 
grains),  combined  with  chloroform  inhalations.  As  much  as  12 
grams  in  twenty-four  hours  were  given  to  some  of  these  cases 
and  the  chloroform  was  administered  until  an  effect  was  secured 
from  the  chloral  hydrate.  Winckel's  series  included  92  cases  with 
a  mortality  of  7,  or  7.6  per  cent.  No  venesection  was  done  in  any 
of  these  cases.  The  results  with  this  method  were  not  invariably 
good  and  later  on  Winckel  modified  the  plan  by  the  addition 
of  various  operative  procedures,  evidently  in  cases  that  did  not 
respond  to  the  more  conservative  procedures. 

The  more  reasonable  employment  of  narcotics  was  suggested 
by  Stroganoff.  Although  not  at  first  entirely  successful,  further 


124 

experience  with  the  method  was  followed  by  better  results,  and  in 
the  last  series  of  360  cases  Stroganoff  reports  a  mortality  of  6.6 
per  cent.  Unfortunately  the  details  of  the  Stroganoff  procedure 
are  not  strictly  followed  by  many  who  claim  to  use  the  method, 
and  the  term  is  applied  in  any  case  where  narcosis  by  morphin 
or  chloral  constitutes  the  essential  factor  in  the  treatment. 
Stroganoff  calls  particular  attention  to  the  necessity  of  placing  the 
woman  in  a  quiet,  darkened  room  and  avoiding  all  forms  of  irrita- 
tion. Examinations,  if  necessary,  should  be  made  under  light 
chloroform  anesthesia.  Another  essential  factor  to  which 
Stroganoff  calls  attention  is  the  necessity  for  beginning  treatment 
before  the  actual  convulsions,  whenever  possible.  In  the  pro- 
cedure described  by  Stroganoff  the  initial  hypodermic  dose  of 
morphin  muriate  is  0.015  gram,  and  one  hour  later  2  grams  of 
chloral  hydrate  are  given  in  solution  in  the  rectum.  Three  hours 
later  the  morphin  is  repeated,  and  four  hours  after  that  the 
chloral.  Thirteen  and  twenty-one  hours  after  the  beginning  of 
treatment  a  dose  of  1.5  grams  of  chloral  hydrate  is  given  by 
rectum.  It  will  be  observed  that  the  interval  between  the  admin- 
istration of  the  drugs  increases  progressively.  The  employment 
of  venesection  is  not  recommended,  but  operative  delivery  may  be 
resorted  to  in  case  the  so-called  prophylactic  treatment  is  partly 
or  wholly  ineffectual.  Such  operations,  however,  Stroganoff 
limits  to  forceps  and  version  under  deep  ether  narcosis.  Cesarean 
section  and  the  introduction  of  the  elastic  bag,  are  not  favored 
except  in  isolated  instances. 

Zweifel  employed  this  procedure  in  his  clinic  at  Leipzig  in  a 
large  number  of  cases,  as  noted  below,  but  combined  it  with 
venesection,  abstracting  not  less  than  500  cubic  centimeters  of 
blood  as  soon  as  the  seizures  began.  In  case  the  seizures  did  not 
seem  to  be  affected  in  number  or  severity  another  venesection 
of  350  cubic  centimeters  was  done.  When  a  second  venesec- 
tion became  necessary  labor  was  always  hastened.  Zweifel 
also  insists  on  thorough  gastric  lavage  in  obstinate  cases,  fol- 
lowed by  the  instillation  of  a  quart  of  weak,  plain  lemonade  or 
cream  of  tartar  lemonade.  Comparing  his  results  with  those 
obtained  before  the  introduction  of  this  method,  Zweifel  reports 
that  when  venesections  with  chloroform  and  morphin  narcosis, 
hot  packs,  etc.  (1887-1892),  were  employed,  the  mortality  in  49 
cases  was  32.6  per  cent.  In  a  series  of  623  cases  treated  by  active 


TREATMENT  125 

operative  methods  from  1895  to  1910  the  total  mortality  was  17.4 
per  cent.  Contrasting  these  results  with  the  period  during  which 
venesection  and  the  Stroganoff  treatment  was  employed,  the  mor- 
tality in  94  cases  fell  to  5.3  per  cent.  The  reduction  in  the  fetal 
mortality  is  also  noteworthy,  having  been  reduced  from  36  per 
cent  in  the  operative  period  to  21.3  per  cent  during  the  time  when 
conservative  methods  were  employed.  Zweifel  discredits  the 
statistics  compiled  by  Liepmann  and  Freund,  who  report  8  deaths 
in  a  series  of  18  cases  at  the  Berlin  Charite  treated  by  the 
Stroganoff  procedure.  He  considers  this  evidence  insufficient  and 
in  comparison  refers  to  their  own  mortality  of  approximately  15 
per  cent  in  the  operative  treatment. 

Comparative  Mortality  Rates. — Winter  also  presents  interest- 
ing comparative  statistics  based  on  the  results  of  the  treatment 
at  his  clinic,  in  which  he  used  exclusively  bloodletting  and  the 
Stroganoff  method  in  order  to  make  a  comparison  with  his  pre- 
ceding methods  of  immediate  delivery.  While  the  conservative 
procedure  is  generally  satisfactory,  Winter  believes  that  imme- 
diate delivery  is  superior  in  recent  cases,  especially  delivery  by 
vaginal  cesarean  section.  On  the  other  hand,  when  a  long-stand- 
ing intoxication  is  present,  the  results  of  immediate  delivery  are 
uncertain  and  the  Stroganoff  method  should  be  preferred.  In 
the  cases  in  which  the  first  convulsion  was  noted  at  the  beginning 
of  labor,  the  results  were  as  follows:  In  8  cases,  in  which  labor 
was  not  interfered  with,  there  was  a  mortality  of  40  per  cent;  in 
19  cases  of  delivery  after  the  os  was  dilated,  30  per  cent  mortality ; 
32  cases  delivered  in  the  second  stage  by  incision  or  bags,  25  per 
cent  mortality;  34  cases  delivered  by  early  vaginal  cesarean  sec- 
tion there  was  9  per  cent  mortality;  in  22  cases  by  cesarean  sec- 
tion immediately  after  the  beginning  of  the  attack,  no  mortality. 

Lichtenstein  also  reports  80  cases  treated  by  venesection  and 
Stroganoff  narcosis  with  5  deaths,  or  6.25  per  cent  mortality.  In 
this  series  many  spontaneous  deliveries  occurred  and  Lichtenstein 
calls  particular  attention  to  the  reduction  in  the  number  of 
attacks,  and  to  the  fact  that  in  60  per  cent  of  the  cases  no  recur- 
rence took  place. 

In  this  country  increasing  attention  is  now  being  given  to  the 
conservative  methods  of  treating  eclampsia,  especially  by  nar- 
cotics. Among  the  most  recent  statistics  is  the  report  by  Mac- 
Pherson  in  an  unpublished  communication,  including  104  cases 


126  TOXEMIAS  OF   PREGNANCY 

with  17  maternal  deaths,  or  a  mortality  of  16.3  per  cent.  These 
patients  were  treated  at  the  New  York  Lying-in  Hospital  and 
included  many  serious  cases,  7  of  which  were  actually  moribund 
on  admission.  Omitting  the  latter,  this  would  make  a  total  mor- 
tality of  only  9.6  per  cent.  The  stillbirth  mortality  was  25.4  per 
cent.  MacPherson  compares  these  figures  with  the  mortality  of 
30.8  in  250  cases  reported  by  him  in  1909  which  were  treated  by 
purely  operative  measures. 

A  more  radical  conception  of  the  treatment  of  eclampsia 
is  that  first  advanced  by  Diihrssen,  who  asserts  that  immediate 
operative  delivery  as  soon  as  possible  after  the  first  seizure  is 
always  indicated.  No  previous  narcosis  was  employed,  for 
Diihrssen  declared  that  chloroform  as  well  as  morphin  con- 
tributed to  fatty  degeneration  of  the  heart  muscle.  As  we  now 
know,  a  simple  degenerative  process  in  the  liver  has  also  been 
shown  to  follow  chloroform  narcosis.  In  order  to  secure  a  rapid 
delivery  Duhrssen  devised  the  operation  known  as  vaginal 
cesarean  section,  although  the  procedure  first  originated  by  him 
included  merely  incision  of  the  anterior  and  posterior  lips  of  the 
cervix.  Attention  was  immediately  attracted  to  the  value  of  this 
procedure  by  Duhrssen,  who  reported  that  in  over  93  per  cent  of 
his  cases,  convulsions  ceased  at  once. 

In  this  country  we  find  Reuben  Peterson  has  been  the  most 
active  advocate  of  the  Duhrssen  type  of  treatment.  He  made  an 
extended  study  of  530  cases  done  by  1 18  operators.  The  collected 
statistics  seem  to  show  that  the  mortality  was  23.4,  which  he  com- 
pared with  an  average  of  28.9  per  cent  after  expectant  treatment. 

The  fetal  mortality  likewise  seemed  to  be  lower,  the  sooner 
delivery  took  place  after  the  first  convulsion.  The  figures  which 
Peterson  presents  of  results  obtained  from  conservative  treat- 
ment certainly  did  not  agree  with  those  presented  elsewhere  and 
he  went  so  far  as  to  state  that  vaginal  cesarean  section  is  simple 
enough  to  be  performed  by  any  one  with  a  fairly  good  knowledge 
of  surgery  and  can  be  carried  out  in  the  home  of  the  patient. 

A  similar  study  subsequently  made  by  the  same  author  is 
interesting  in  this  connection.  This  later  collection  of  statistics 
included  500  cases  of  abdominal  cesarean  section  for  eclampsia 
representing  the  work  of  259  operators  both  here  and  abroad.  In 
order  to  show  the  improvement  in  results  Peterson  grouped  the 
cases  chronologically.  Between  1908  and  1913  there  were  283 


TREATMENT  127 

cases  with  73  deaths  or  a  maternal  mortality  of  25.79  Per  cent. 
Up  to  1908  there  were  198  cases  with  95  deaths,  or  a  mortality 
of  47.97  per  cent.  This  shows  a  reduction  in  the  maternal  mor- 
tality of  almost  one  half  and  is  a  reason,  according  to  Peterson, 
why  we  should  label  as  incorrect  the  older  figures  of  a  50  per  cent 
maternal  mortality  from  abdominal  cesarean  section  for  eclamp- 
sia. He  believes  that  the  present  mortality  rate  can  be  consider- 
ably lowered  by  care  in  technic  and  avoiding  potentially  infected 
cases.  Although  an  eclamptic  patient  may  die  after  a  single  con- 
vulsion, or  may  survive  many  convulsions,  Peterson  claims  that 
the  latter  fact  must  be  utilized  as  an  indication  of  the  degree  of 
eclamptic  poisoning  until  we  have  a  better  method  of  estimation. 
Emptying  the  uterus  either  spontaneously  or  by  artificial  means, 
while  it  puts  a  stop  to  the  further  elaboration  of  toxins  from  the 
fetus,  the  placenta,  or  both,  may  not  be  sufficient  to  prevent 
further  convulsions,  or  in  certain  cases  the  death  of  the  mother 
from  intoxication. 

In  the  1914  Peterson  series,  convulsions  ceased  after  abdom- 
inal cesarean  section  in  251  out  of  457  cases,  or  in  54.92  per  cent. 
This  is  in  agreement  with  the  general  view  that  convulsions  cease 
after  the  uterus  is  emptied  in  from  52  to  62  per  cent  of  the  cases. 
In  146  cases  in  which  convulsions  ceased  after  cesarean  section 
there  were  41  deaths,  or  19.8  per  cent  mortality.  This  figure  is 
said  to  be  much  lower  than  when  the  convulsions  continue,  since 
in  130  of  such  cases  there  were  41  deaths,  or  a  maternal  mortality 
of  31.53  per  cent.  Peterson  insists  that  the  operative  treatment 
of  eclampsia  has  not  been  given  a  fair  trial,  for  the  uterus  should 
be  emptied  as  soon  as  possible  after  the  onset  of  the  first  convul- 
sion and  not  after  all  kinds  of  medicinal  treatment  have  been  tried 
and  failed.  He  finds  an  increase  in  mortality  of  30.33  per  cent 
due  to  delay,  which  is  10  per  cent  higher  than  after  quick  delivery. 
As  regards  the  fetal  mortality  in  Peterson's  series,  including  all 
premature  children  and  counting  all  children  as  living  who  sur- 
vived one  hour  after  delivery,  there  were  9  deaths  in  248  cases,  or 
3.62  per  cent.  The  fetal  mortality,  however,  was  10.69  per  cent 
if  children  dying  the  first  three  days  after  delivery  be  included. 
He  believes,  therefore,  that  better  results  are  obtained  for  the 
fetus  if  the  uterus  is  emptied  early. 

Peterson  found  that  the  maternal  mortality  is  higher  in 
cesarean  section  cases  in  multiparous  women  than  in  primiparous 


128  TOXEMIAS  OF   PREGNANCY 

eclamptics.  In  225  primiparae  the  maternal  mortality  was  24.44 
per  cent,  while  in  48  multiparae  it  was  27.08  per  cent.  The  fetal 
mortality  was  also  increased,  which  he  attributes  to  the  greater 
degree  of  intoxication  among  multiparae.  The  maternal  mor- 
tality also  increases  with  the  age  of  the  patient.  Peterson  con- 
cludes that  any  obstetric  condition  which  makes  delivery  by  the 
natural  passage  prolonged  and  difficulty,  may  be  accepted  as  an 
indication  for  abdominal  cesarean  section  in  eclampsia,  although 
it  cannot  be  denied  that  other  methods  of  emptying  the  uterus 
give  better  results  in  eclamptics  with  normal  pelves  and  soft  parts 
and  should  not,  therefore,  be  lightly  discarded. 

Cesarean  Section,  When  Justifiable. — Whether  abdominal 
cesarean  section  is  justifiable  in  eclampsia  has  been  questioned  in 
a  number  of  later  contributions.  Thus,  Brodhead  contends  that 
in  a  large  proportion  of  cases  it  should  not  be  employed,  although 
when  the  facilities  are  at  hand  it  affords  a  satisfactory  means  of 
terminating  the  case.  He  collected  174  selected  cases  of  cesarean 
section  for  eclampsia  with  a  mortality  of  28,  or  16.1  per  cent. 
This  included  one  case  each  of  sepsis,  pneumonia,  intestinal  ob- 
struction, ruptured  uterus,  and  simple  neglect.  Subtracting  these 
cases,  the  mortality  was  12.2  per  cent.  There  were  154  living 
children,  of  which  29  subsequently  died,  including  premature  and 
poorly  nourished  infants.  In  a  later  edition  of  39  unpublished 
cases  the  mortality  was  15.4  per  cent,  making  a  total  of  213  sec- 
tions with  34  deaths,  or  16  per  cent. 

It  is  a  difficult  matter  to  form  an  absolute  opinion  as  to  the 
value  of  either  vaginal  or  cesarean  section  in  eclampsia.  Un- 
doubtedly the  fetal  mortality  is  lowered,  especially  if  the  opera- 
tion can  be  performed  soon  after  the  first  convulsion,  but  as  these 
babies  are  often  poorly  nourished  or  develop  toxic  symptoms  sub- 
sequently, the  fetal  death  rate  during  the  first  few  weeks  should 
be  taken  into  consideration.  Moreover,  operative  deliveries  of 
all  kinds  in  eclampsia  are  productive  of  shock,  and  if  shock  be 
combined  with  excessive  hemorrhage,  the  subsequent  recovery  of 
the  patient  is  often  doubtful.  The  operation  with  our  modern 
methods  is  simple  enough  and  has  often  been  attempted  by  the 
tyro  in  obstetrics.  My  own  belief  is  that  it  should  be  limited,  as  I 
have  already  stated,  to  primiparae  at  term  with  long  rigid  cervices 
that  show  no  tendency  to  dilatation,  combined  with  slightly  con- 
tracted pelves  and  a  rigid  or  perhaps  narrowed  outlet.  With  a 


TREATMENT  129 

patient  in  good  general  condition  who  passes  urine  at  least  in 
moderate  amounts,  although  not  responding  to  the  narcotic  treat- 
ment after  the  first  convulsion,  it  seems  to  me  that  the  psychic 
factor  enters  into  the  question  and  that  the  doctor  and  family  in 
many  instances  are  overcome  with  a  feeling  of  fear  caused  by  the 
severity  of  the  clinical  picture,  and  lose  to  some  degree,  perhaps, 
their  sense  of  calm  and  better  judgment.  Cesarean  sections, 
either  vaginal  or  abdominal,  should  not  be  undertaken  except 
under  the  most  satisfactory  hospital  surroundings,  and  the 
increasingly  good  results  reported  with  more  conservative 
methods  should  always  be  taken  into  consideration  in  deciding 
what  shall  be  done  in  an  individual  case. 

Venesection. — This  is  one  of  the  oldest  procedures  in  the 
treatment  of  eclampsia.  As  I  noted  in  the  historical  introduction, 
medical  writers  for  centuries  have  advocated  opening  an  artery 
or  a  vein  for  the  relief  of  convulsions,  on  the  supposition  that  an 
overdistention  of  the  blood-vessels  was  present,  as  manifested  by 
the  increased  pulse  tension,  cyanosis  and  coma.  In  place  of  the 
actual  opening  of  the  vein,  leeches  applied  to  various  parts  of  the 
head  and  body  were  formerly  employed  in  some  cases  and 
believed  to  be  particularly  adapted  to  the  more  anemic  type  of 
women.  The  introduction  of  chloroform  brought  about  a  change 
in  the  views  on  this  subject  and  venesection  came  to  be  regarded 
as  harmful  because  the  convulsions  were  ascribed  to  cerebral 
anemia.  After  this  theory  was  shown  to  be  groundless,  venesec- 
tion returned  to  favor,  especially  as  the  mortality  in  various  clinics 
was  found  to  increase  during  the  period  when  no  venesection  was 
employed  and  before  other  methods  of  treatment  were  developed. 
As  the  rapid  operative  deliveries  came  into  vogue  the  assertion 
was  repeatedly  made  that  it  was  not  the  operation  of  itself,  nor 
the  rapid  emptying  of  the  uterus  that  brought  about  a  good 
result,  but  merely  the  loss  of  blood.  The  abstraction  of  from  300 
to  500  cubic  centimeters  of  blood  from  an  arm  vein  in  suitable 
cases  is  very  generally  employed,  but  according  to  the  best  teach- 
ing, it  should  be  reserved  for  the  cases  of  plethoric  women  in 
whom  no  improvement  results  after  thorough  narcotization  has 
been  secured.  Thin,  weak,  anemic-looking  patients  should,  under 
no  circumstances,  be  subjected  to  venesection  even  when  the 
blood-pressure  is  high.  In  post-partum  attacks  the  abstraction 
of  blood  has  been  favorably  regarded  by  many  as  a  life-saving 


130  TOXEMIAS  OF   PREGNANCY 

measure,  but  its  employment  at  this  time  should,  it  seems  to  me, 
be  subjected  to  the  same  criteria  as  during  the  ante-partum  period. 

TECHXIC  OF. — Venesection  in  eclampsia  is  preferably  done  in  the 
median  cephalic  or  basilic  veins.  The  patient,  if  not  in  a  nar- 
cotized state,  should  be  given  a  few  whiffs  of  ether  and,  after 
applying  a  tourniquet  to  the  upper  arm,  a  coating  of  tincture  of 
iodin  is  painted  on  the  flexor  surface  of  the  elbow,  the  vein  is 
exposed  by  incising  the  skin  over  the  same  and  a  canula  inserted 
and  tied.  A  simpler  procedure  is  to  introduce  a  good-sized  hypo- 
dermic needle  or  small  trocar  directly  into  the  vein.  The  needle 
or  canula  is  very  apt  to  become  obstructed  at  the  beginning  of  the 
flow,  by  clots,  and  should  then  be  withdrawn  and  cleaned  with 
sterile  water  or  salt  solution. 

Decapsulation  of  the  Kidney. — The  conception  of  eclampsia 
as  a  disease  in  certain  cases  of  renal  origin,  led  to  a  proposal  by 
G.  M.  Edebohls  to  relieve  the  anuria  by  a  decapsulation  operation 
on  the  kidney.  His  first  patient,  a  primipara,  with  severe  repeated 
convulsions  was  delivered  under  chloroform  by  forceps  after 
cervical  incision.  Post-partum  convulsions  and  coma  continued 
without  response  to  the  usual  treatment  in  vogue  and,  "for  the 
purpose  of  obtaining  control  of  the  uremia,"  decapsulation  of 
both  kidneys  was  performed  three  days  after  delivery.  No  further 
convulsions  occurred  and  two  days  later  all  evidences  of  "uremia" 
disappeared  with  a  complete  restoration  to  health  in  a  few  weeks. 
Edebohls  was  so  impressed  by  the  result  that  he  advocated  the 
procedure  before  labor.  A  second  case  was  operated  upon  a  year 
later,  also  in  a  primipara,  with  marked  edema,  alternating  delir- 
ium and  coma,  total  blindness,  almost  complete  anuria  and  begin- 
ning convulsions.  Double  renal  decapsulation  was  performed, 
followed  by  great  improvement  in  symptoms,  and  labor  came  on 
spontaneously  forty-eight  hours  after  operation  with  delivery  of 
twins. 

CASE  REPORTS  OF. — This  somewhat  radical  procedure  met  with 
considerable  attention  after  its  publication.  Sippel  reported  42 
cases  with  12  deaths  (28  per  cent),  a  rather  high  mortality  rate, 
but  an  anuria  persisting  for  several  hours,  as  in  these  cases,  is 
usually  fatal.  In  3  cases  reported  by  Zweifel,  recovery  took  place 
and  the  urinary  excretion  underwent  a  satisfactory  and  constant 
increase  soon  after  the  operation.  A  more  recent  report  is  by 
Cardwell,  who  did  a  decapsulation  and  nephrotomy  three  days 


TREATMENT  131 

after  delivery  in  a  patient  with  severe  convulsions.  Immediate 
improvement  resulted. 

The  Edebohls'  operation,  while  radical,  may  perhaps  be  of 
service  in  those  severe  cases  in  which  anuria  develops,  but  with 
the  introduction  of  the  other  and  newer  methods  of  treating 
eclampsia  the  indications  are  not  so  frequently  met  with.  If  the 
decapsulation  operation  is  decided  upon  in  one  of  these  serious 
cases,  the  kidneys  are  exposed,  first  one  and  then  the  other, 
through  incisions  along  the  outer  margin  of  the  erector  spinae 
from  the  twelfth  rib  to  the  crest  of  the  ilium,  with  the  patient 
prone  and  the  abdomen  supported  by  an  Edebohls'  "kidney 
cushion."  The  fibers  of  the  latissimus  dorsi  are  then  separated 
and  the  iliohypogastric  nerve  isolated  and  drawn  to  one  side.  The 
transversalis  fascia  is  divided,  the  perirenal  fat  incised,  and  the  kid- 
ney delivered  if  possible.  The  capsule  is  divided  along  the  entire 
convex  border  of  the  kidney  and  stripped  completely  free  with  the 
gloved  finger,  after  which  it  is  cut  away  close  to  the  pelvis.  The 
kidney  is  dropped  back  into  its  fatty  capsule  and  the  wound 
closed,  usually  without  drainage. 

Skull  Trephining  and  Lumbar  Puncture.  —  Among  other 
operative  measures  employed  in  eclampsia  aside  from  delivery, 
mention  may  be  made  of  the  skull  trephining  procedure  suggested 
by  Zangemeister  for  the  relief  of  intracranial  pressure.  In  these 
cases  a  large  osteoplastic  flap  was  made,  but  the  good  results 
reported  were  not  confirmed  by  others.  It  would  appear  that  the 
same  effect  could  be  achieved  by  lumbar  puncture  and  this  has 
frequently  been  resorted  to,  from  5  to  10  cubic  centimeters  of 
cerebrospinal  fluid  being  withdrawn.  Among  more  recent  reports, 
J.  M.  Snyder  describes  a  case  of  severe  eclamptic  convulsions  in  a 
primipara  twenty-five  years  of  age  in  active  labor,  delivered  by 
low  forceps.  Sedative  and  eliminant  treatment  was  employed, 
but  numerous  severe  convulsions  continued  with  high  temper- 
ature and  rapid  respiration.  The  patient  was  almost  moribund 
when  a  lumbar  puncture  was  done,  and  about  two  drachms  of 
fluid  allowed  to  escape.  It  was  not  under  pressure  and  perfectly 
clear.  Immediate  improvement  in  the  general  appearance  of  the 
patient  resulted,  the  cyanosis  disappeared,  the  respirations  became 
more  regular  and  deeper  and  the  edema  slowly  subsided.  No 
further  convulsions  occurred  and  the  patient  made  a  steady 


132  TOXEMIAS  OF  PREGNANCY 

recovery,  presenting  a  normal  temperature  on  the  third  day  with 
a  return  of  consciousness. 

MAGNESIUM  SULPHATE,  IN  LUMBAR  PUNCTURE. — As  an  acces- 
sory to  lumbar  puncture,  the  injection  of  magnesium  sulphate  or 
of  pregnancy  serum  has  been  recommended.  Rissmann,  who  was 
probably  the  first  to  suggest  the  method,  believed  that  the  toxins 
of  eclampsia  involve  primarily  the  cord  and  brain  and,  acting  like 
tetanus,  can  be  similarly  affected  by  magnesium  sulphate.  In  his 
first  case,  a  primipara,  the  convulsions  persisted  after  the  birth  of 
the  child  but  ceased  at  once  after  the  intradural  injection  of  5 
cubic  centimeters  of  a  15  per  cent  solution  of  magnesium  sulphate 
in  sterile  water.  In  a  contemporary  article,  Guggisberg  denies 
the  harmlessness  of  the  procedure,  and  shows  that  the  action  of 
the  drug  in  eclampsia  is  different  from  that  in  tetanus.  More- 
over, in  order  to  obtain  an  effect,  the  magnesium  sulphate  must 
be  injected  at  a  higher  level  in  the  cord,  which,  while  it  may 
reduce  the  convulsions,  is  apt  to  have  a  dangerously  paralyzing 
effect  on  the  respiration.  Both  of  Guggisberg's  cases  ended 
fatally,  although  in  the  second  one,  where  the  injection  site  was 
higher,  the  sedative  effect  on  the  convulsions  was  marked.  Wal- 
lace advocated  a  25  per  cent  sterilized  solution  of  magnesium 
sulphate  administered  according  to  the  weight  of  the  patient,  in 
the  proportion  of  I  cubic  centimeter  to  every  twenty-five  pounds. 
He  reported  two  cases,  the  first  of  which  recovered  after  one 
injection  and  the  second  after  two.  Wallace  also  warns  against 
the  possible  paralyzing  effect  on  the  respiratory  center. 

NORMAL  PREGNANCY  SERUM. — In  place  of  the  magnesium  sul- 
phate injection,  Mayer  suggested  normal  pregnancy  serum  as  an 
antidote  to  the  poison  circulating  in  the  central  nervous  system. 
This  author  reports  two  cases  of  advanced  coma  with  pulmonary 
edema  and  history  of  convulsions.  The  prognosis  was  very  bad 
but  nevertheless  the  serum  was  given.  In  one  case  the  patient 
apparently  made  a  complete  recovery,  but  in  the  other  the  disease 
was  evidently  too  far  advanced  and  the  patient  died  soon  after. 
In  another  instance,  the  baby  of  a  mother  who  had  had  a  mild 
eclampsia  was  seized  with  severe  convulsions.  Five  cubic  centi- 
meters of  spinal  fluid  was  withdrawn  and  an  equal  amount  of 
blood  serum  of  a  healthy  pregnant  woman  injected.  An  imme- 
diate change  for  the  better  occurred  and  the  convulsions  ceased, 


TREATMENT  133 

hut  the  child  died  several  hours  later,  apparently  from  cardiac 
weakness. 

Rectal  Infusions  of  Magnesium  Sulphate. — To  return  for  a 
moment  to  the  antitetanic  action  of  magnesium  sulphate,  we  may 
refer  to  the  rectal  and  subcutaneous  methods  of  administration. 
Rissmann  also  suggested  this  method,  combining  the  sulphate 
with  veronal  or  luminal.  He  declared  that  morphin  is  contra- 
indicated  because  of  the  danger  to  the  fetal  respiratory  center, 
and  chloral  because  it  is  a  cellular  poison.  Six  cases  are  reported 
in  which  luminal  in  doses  of  0.04  gram  injected  subcutaneously 
either  alone  or,  in  the  more  severe  cases,  combined  with  rectal 
infusions  of  magnesium  sulphate  (from  10  to  15  grams  to  the 
liter),  brought  about  a  rapid  subsidence  of  the  convulsions  and 
complete  recovery. 

Blood  Transfusion. — On  the  theory  that  there  is  a  substance 
in  normal  blood  which  neutralizes  the  toxins  of  the  placenta,  the 
transfusion  of  blood  has  been  recommended  in  eclampsia.  Blair 
Bell,  almost  a  decade  ago,  reported  a  severe  case  in  a  primipara, 
in  whom  immediate  improvement  followed  the  intravenous  injec- 
tion of  500  cubic  centimeters  of  the  husband's  blood.  He  claimed 
that  transfusion  is  the  best  means  of  introducing  antitoxins,  which 
are  also  present  in  the  blood  of  males. 

Ductless  Glandular  Opotherapy  and  Serotherapy. — The  belief 
that  disturbances  in  the  endocrine  glands  are  etiological  factors 
in  the  production  of  eclampsia  has  served  as  the  basis  for  many 
therapeutic  recommendations.  It  is  essential  to  approach  the 
problem  with  a  great  deal  of  caution.  The  thyroid  is  an  example 
when  decision  as  to  whether  one  is  dealing  with  hypo-  or  hyper- 
thyroidism  might  better  be  left  to  an  expert  rather  than  deter- 
mined by  the  obstetrician,  unless  the  latter  has  been  specially 
trained  to  recognize  the  symptoms  associated  with  these  more  or 
less  obscure  conditions.  Where  a  lack  of  thyroid  secretion  is 
evident,  E.  P.  Davis  advises  small  doses  of  the  extract,  one  grain 
three  times  daily,  continued  for  several  months.  Ward  states  that 
it  is  essential  when  Graves'  disease  is  present,  to  determine 
whether  it  is  a  condition  of  hyperthyroidism  or  hypothyroidism. 
In  the  former,  rest,  icebags,  milk  diet,  and  sedatives  should  be 
employed,  and  if  these  measures  fail,  an  antiserum,  such  as  the 
cytotoxic  serum  of  Rogers,  may  be  administered.  If  hypo- 
thyroidism is  present,  thyroid  substance  should  be  given  in  the 


i34  TOXEMIAS  OF  PREGNANCY 

form  of  the  dry  extract,  or,  if  possible,  a  saline  extract  prepared 
from  normal  human  glands.  Ward  believes  that  more  reliance 
can  be  placed  upon  the  nitrogen-partition  of  the  urine  as  a  guide 
to  the  severity  of  the  toxemia  than  on  the  blood-pressure.  Since 
this  was  written,  however,  the  view  as  to  the  value  of  the  nitro- 
gen-partition test  has  undergone  a  marked  change.  Induction 
of  labor  is  usually  slow  and  uncertain  in  such  cases,  and,  where 
there  is  a  history  of  dystocia,  elective  cesarean  section  is  prefer- 
able. 

Although  parathyroid  extracts  have  been  urged  in  the  treat- 
ment of  eclampsia  because  of  the  changes  which  these  glands 
undergo  in  pregnancy,  there  is  no  warrant  for  this  view  because, 
as  pointed  out  long  ago  by  Seitz,  the  tetany  produced  by  the 
removal  of  the  parathyroids  in  pregnant  animals  is  not  necessarily 
tru:  same  as  eclampsia. 

Anomalies  in  placental  function  as  a  cause  for  eclampsia 
have  been  regarded  as  indications  of  hysterectomy  (Zange- 
meister),  and  the  "mammary  theory"  encouraged  several  Ger- 
man observers  to  propose  complete  ablation  of  the  breasts  for 
the  relief  of  eclampsia  (Sellheim,  Herrenschneider,  and  Wagner), 
but  these  are  extremist  measures,  no  longer  warranted  in 
view  of  the  good  results  which  have  attended  less  radical  methods 
of  treatment.  The  milking  out  of  the  colostrum  from  the  breasts 
and  also  the  intramammary  injection  of  air  or  oxygen  have  been 
seriously  proposed  in  treating  eclampsia..  These  references  are 
of  interest,  but  much  remains  to  be  learned  before  such  treatment 
can  be  satisfactorily  employed. 

Flushing  through  the  Stomach. — The  introduction  of  fluid 
into  the  circulation  for  the  purpose  of  diluting  the  circulating 
toxins,  throwing  off  the  excess  of  salts  and  reducing  the  molecular 
concentration  of  the  blood,  is  considered  an  essential  of  treatment, 
and  in  this  connection  we  may  refer  to  an  interesting  suggestion 
for  flushing  the  system  recently  made  by  Davidson.  In  place  of 
hot  packs  and  irrigations,  from  two  to  three  pints  of  water  are 
administered  through  the  stomach  tube  every  four  hours.  In 
eleven  cases  this  procedure  was  followed  by  profuse  perspiration, 
and  it  can  be  done  at  home  where  efficient  hot  packs  are  often 
impossible.  A  far  larger  amount  of  fluid  may  be  introduced  than 
by  the  customary  methods  and  satisfactory  catharsis  stimulated 
without  resort  to  other  measures.  Regurgitation  and  aspiration 


TREATMENT  135 

have  not  been  noted  but  the  water  should  be  introduced  quite 
rapidly  and  the  tube  removed  at  once.  There  is  apparently  no 
danger  from  acute  gastric  dilatation.  The  stomach  was  found  to 
empty  itself  quite  rapidly,  no  water  being  recovered  when  the 
tube  was  introduced  four  hours  later.  Davidson  believes  that  in 
these  cases  we  are  dealing  with  a  "toxic  kidney  block"  rather  than 
a  true  nephritis,  and  'that  the  fluids  introduced  through  the 
stomach  are  excreted  by  the  kidneys  more  rapidly  than  if  intro- 
duced into  the  rectum  or  intravenously,  or  into  the  tissues.  He 
states  that  in  cases  where  as  little  as  two  ounces  of  urine  was 
secured  by  catheter  at  the  beginning  of  treatment,  thirty-two 
ounces  were  obtained  eight  hours  later  and  a  total  of  over  one 
hundred  and  twenty  ounces  during  the  first  twenty-four  hours. 
With  this  treatment  he  also  advises  the  administration  of  an  ounce 
or  an  ounce  and  a  half  of  Epsom  salts  and  some  alkali,  such  as 
twenty  grains  of  potassium  acetate  or  citrate,  each  time  the  tube 
is  passed.  Very  possibly  the  latter  have  a  pronounced  diuretic 
effect.  Davidson  suggests  that  at  least  three  lavages  be  done  even 
after  the  patient  is  apparently  out  of  the  critical  state. 

Carbohydrates. — The  employment  of  carbohydrates  in  the 
treatment  of  the  toxemias  of  pregnancy  has  constituted  one  of  the 
important  developments  of  recent  years  in  the  management  of 
this  class  of  cases.  The  so-called  carbohydrate  deficiency  theory 
is  based  on  the  assumption  that  the  liver  is  the  carbohydrate 
storing  organ  of  the  body  and  its  cells  filled  with  glycogen  and 
that  a  carbohydrate  deficiency  in  the  maternal  organism  causes 
a  glycogen  depletion  of  the  liver.  Such  a  deficiency  of  carbo- 
hydrates during  pregnancy  may  be  of  twofold  origin:  (i)  there 
is  an  unexpected  demand  for  glycogen  on  the  part  of  the  fetus,  as 
shown  by  Slemons  and  others,  and  to  a  lesser  degree  by  the  rapid 
hypertrophy  of  the  uterus;  and  (2)  an  actual  deficiency,  aug- 
mented in  the  presence  of  nausea  and  vomiting  from  lessened 
carbohydrate  intake  as  the  result  of  an  improperly  balanced  diet. 
Titus  and  Givens,  of  Pittsburgh,  have  recently  presented  experi- 
mental evidence  in  an  attempt  to  show  that  the  liver  function  is 
impaired,  especially  in  its  detoxicating  properties,  and  the  body 
flooded  with  toxins  after  carbohydrate  starvation.  In  other 
words,  that  a  circulating  poison  is  more  toxic  to  an  animal  which 
has  been  fed  low  in  carbohydrates.  It  was  also  found  that  the 
toxic  effect  of  any  poison  is  markedly  diminished  if  given  simul- 


136  TOXEMIAS  OF  PREGNANCY 

taneously  with  a  dose  of  glucose.  The  favorable  effects  of 
excessive  carbohydrate  feeding  in  the  vomiting  of  pregnancy  has 
already  been  referred  to  in  a  previous  paragraph,  and  in  the 
more  serious  cases  intravenous  injections  of  carbohydrates  in 
the  form  of  glucose  solution  are  known  to  give  striking  results. 
Titus  reports  in  a  more  recent  paper  a  series  of  144  cases  of 
rvomiting  of  pregnancy,  including  26  of  the  pernicious  type,  in 
which  good  results  were  thus  secured  and  in  only  two  was  it 
necessary  to  perform  an  abortion.  One  of  these  was  a  fatal  case 
and  stated  to  be  typical  of  acute  yellow  atrophy  of  the  liver.  The 
same  authors  have  now  extended  this  method  to  the  toxemias  of 
later  pregnancy,  and  report  a  series  of  20  cases  in  which  intra- 
venous injections  of  glucose  were  used  in  addition  to  a  plan  of 
treatment  which  may  be  denominated  conservative,  including  the 
use  of  morphin,  gastric  lavage,  purges,  colonic  irrigations  and 
venesection,  limiting  interference  with  the  pregnancy  only  when 
the  patient's  condition  was  improved  or  the  fetus  could  be  deliv- 
ered without  undue  shock  to  the  mother.  In  this  series  there 
were  three  deaths,  a  mortality  of  15  per  cent,  whereas  the  rate 
previously  with  similar  treatment  but  without  the  glucose  injec- 
tions had  been  about  29  per  cent  in  the  same  hospital  service. 

In  order  to  appreciate  more  fully  the  basis  underlying  the 
claims  of  Dr.  Titus  for  the  method,  it  is  necessary  to  quote  him 
somewhat  more  extensively: 

"We  maintain,"  he  states,  "that  the  pathologic  progress  of 
toxemia  is  dependent  on  a  carbohydrate  deficiency  in  the  ma- 
ternal organism,  particularly  in  respect  to  the  impairment  of 
physiologic  activity  of  the  liver  when  unduly  depleted  of  glyco- 
gen.  It  is  indisputable,  whatever  the  actual  source  of  the  toxins 
of  pregnancy,  that  the  liver  and  its  functions  plan  an  important 
part  in  the  patient's  ability  or  inability  to  recover.  This  is  readily 
confirmed  both  clinically  and  pathologically,  and,  indeed,  the  dis- 
tinctive pathology  of  certain  necrotic  lesions  in  the  liver  has  been 
considered  pathognomonic  of  various  types  of  toxemia  of  preg- 
nancy. Williams  says,  for  instance,  that  peripheral  necrosis  of 
the  liver  lobules  is  the  lesion  to  be  found  in  fatal  cases  of  eclamp- 
sia, whereas  central  necrosis  is  to  be  expected  of  acute  yellow 
atrophy  of  the  liver  and  pernicious  vomiting  of  pregnancy.  The 
entire  distinctiveness  of  these  lesions  has.been  open  to  some  ques- 


TREATMENT 


137 


tion  in  that  there  seems  to  be  considerable  diversity  of  opinion 
among  such  writers  as  De  Lee,  Hirst,  Bumm,  Berkeley  and 
Bonney,  and  others  regarding  the  pathology  of  eclampsia.  Cer- 
tain of  our  specimens  from  fatal  cases  of  eclampsia  have  shown 
a  predominance  of  peripheral  degeneration,  but  central  lobular 
changes  also  are  clearly  evident.  The  reverse  is  true  of  specimens 


FIG.  27. — SECTION  OF  KIDNEY  OF  DOG  (Xso)  SUBJECTED  TO  CHLOROFORM  ANESTHESIA 
ON  THREE  SUCCESSIVE  DAYS  OR  A  TOTAL  PERIOD  OF  FIFTEEN  HOURS.  Finally 
killed  with  chloroform  on  the  fifth  day.  Stained  to  show  the  extensive  fatty 
degeneration  (Hull). 

from  cases  of  vomiting  of  pregnancy,  in  that  the  central  necrosis 
is  accompanied  by  a  certain  amount  of  peripheral  degeneration 
of  the  lobules.  This  may  be  due  entirely  to  relational  differences 
between  specimens;  but,  be  that  as  it  may,  it  is  quite  natural  in 
any  toxemia  to  expect  both  clinical  and  pathologic  involvement 
of  what  is  known  to  be  the  great  detoxicating  organ  of  the  body. 
As  a  matter  of  fact,  pathologic  changes  are  evident  in  the  liver 


138  TOXEMIAS  OF  PREGNANCY 

lobules  after  a  lethal  dose  of  almost  every  poison,  whether  it  be 
organic  or  metallic. 

"It  is  not  intended  to  lose  sight  of  the  disturbances  in  kidney 
function  which  are  almost  invariable  in  eclampsia  and,  to  a  lesser 
degree,  in  other  toxemias  of  pregnancy,  but  it  is  possible  that  they 
may  be  incidental  to  the  action  of  these  toxins  as  they  are  in 
pratically  all  cases  of  poisoning  of  any  nature.  For  example, 


FIG.  28. — SECTION  OF  KIDNEY  OF  DOG  (Xso)  AFTER  SEVEN  AND  ONE-HALF  HOURS 
OF  CHLOROFORM  ANESTHESIA,  SHOWING  MARKED  CONGESTION  WITH  CLOUDY 
SWELLING  AND  HEMORRHAGES  INTO  THE  PARENCHYMA.  Fatty  degeneration  is 
also  pronounced  (Hull). 

nephritis  occurs  in  the  course  of  scarlet  fever  or  pneumonia  or 
after  mercuric  chlorid  poisoning,  as  readily  and  as  definitely  as  in 
hyperemesis  gravidarum." 

Intravenous  Injection  of  Glucose. — Titus  and  Givens  attempt 
to  prove  the  claim  that  the  damaged  liver  cells  are  restored  to  a  marked 
degree  by  the  intravenous  injection  of  glucose  by  a  series  of 


TREATMENT  139 

photomicrographs  of  sections  of  liver  from  certain  fatal  cases. 
These  are  compared  with  a  section  from  an  untreated  case  of 
eclampsia  (see  Figs.  27-30).  It  is  claimed  that  the  liver  tissue  from 
patients  who  received  glucose  intravenously  shows  far  less  patho- 
logic change  than  is  ordinarily  to  be  demonstrated,  the  lobules 
presenting  in  many  instances  a  fairly  normal  appearance.  It  is 
already  well  known  that  the  regenerating  powers  of  the  normal 
liver  are  considerable. 


FIG.  29. — SECTION  OF  LIVER  OF  DOG  (Xso)  AFTER  Two  HOURS  OF  CHLOROFORM 
ANESTHESIA.  The  liver  appears  yellow  and  fatty,  with  scattered  hemorrhages. 
The  cells  about  the  centers  of  the  lobules  are  entirely  necrotic,  a  granular  mass 
remaining.  In  some  cases  the  liver  cells  almost  entirely  disappear  with  only  a 
few  scattered  living  cells  in  the  portal  spaces  (Hull). 

The  technic  of  the  preparation  and  injection  of  the  glucose 
solution  is  very  important,  and,  in  addition,  Titus  believes  that 
the  determination  of  the  blood-sugar  at  definite  intervals  makes 
it  possible  to  plot  a  glycemia  curve  which  is  of  prognostic  value. 
It  is  essential  that  the  glucose  be  of  the  highest  purity.  The  fil- 


140  TOXEMIAS  OF  PREGNANCY 

tered  solution  must  be  sterilized  under  fifteen  pounds  pressure  for 
thirty  minutes.  The  amount  of  glucose  injected  varied  from  15 
to  75  grams  dissolved  in  from  300  to  500  cubic  centimeters  of 
water — approximately  a  15  per  cent  solution.  The  flow  must  be 
regulated  so  that  the  entire  volume  is  introduced  in  about  thirty 
minutes — the  ordinary  salvarsan  apparatus  with  a  clamped  tube 
being  sufficient  for  the  purpose. 


FIG.  30. — SECTION  OF  LIVER  FROM  A  CASE  OF  TOXEMIA  AFTER  INTRAVENOUS  GLUCOSE 
INJECTION.  This  section  shows  several  "foamy"  patches  with  normal  tissue 
separating  them.  There  is  very  little  necrosis  present  and  these  areas  are  not 
well  defined,  being  surrounded  by  numerous  large  cells  with  large,  darkly  staining 
nuclei,  evidently  a  recent  reparative  process.  This  and  the  following  illustrations 
(Figs.  31,  32,  33,  personally  contributed  by  Dr.  Titus)  seem  to  show  that  the 
typical  necrosis  associated  with  acute  yellow  atrophy  and  eclampsia  is  altered 
where  intravenous  injections  of  glucose  have  been  employed. 

Glycemia  Curve  as  Index  to  Liver  Impairment. — A  further 
reference  to  the  glycemia  curve  as  an  index  of  liver  impairment 
may  be  made.  Titus  and  Givens  believe  that  the  degree  or  extent 
of  liver  impairment  in  the  presence  of  toxemia  can  be  determined 


TREATMENT 


141 


by  this  means.    Briefly  outlined  the  steps  are  as  follows  and  I  am 
quoting  them  extensively  for  obvious  reasons. 

"A  specimen  of  blood  is  taken  for  a  blood-sugar  determination, 
and  a  given  amount  of  glucose  is  injected  intravenously,  taking 
a  definite  length  of  time  for  the  injection,  after  which  another 
specimen  is  taken  for  blood-sugar  estimation.  Blood-sugar  read- 


FIG.  31. — SECTION  OF  LIVER  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  SWOLLEN  CELLS, 
POORLY  OUTLINED,  COARSELY  PIGMENTED.  Irregularity  in  size  is  noteworthy 
and  the  large  amount  of  protoplasm  suggests  a  process  of  repair  (Titus). 

ings  follow  at  stated  intervals  and  from  them  a  glycemia 
curve  may  be  plotted.  It  was  thought  that  the  rate  of  absorption 
and  storage  of  the  injected  sugar  would  give  an  idea  of  the  con- 
dition of  the  liver  in  the  following  respects:  A  liver  depleted  of 
glycogen  but  not  infiltrated  with  fat  should  be  greedy  for  sugar 
and  take  it  up  from  the  blood  stream  at  a  rate  faster  than  under 
normal  circumstances,  whereas  a  liver  which  had  undergone  fatty 


142 


TOXEMIAS  OF   PREGNANCY 


infiltration  and  necrosis  would  probably  have  its  function  in  this 
respect  impaired,  even  though  it  were  more  urgently  in  need  of 
glycogen.  It  should  be  particularly  pointed  out  that  the  glucose 
is  injected  primarily  for  its  therapeutic  effect  rather  than  for  the 
sake  of  this  glycemia  test,  and  that  the  taking  of  blood  specimens 
involves  no  loss  of  valuable  time  in  these  serious  and  rapidly 
progressing  pathologic  conditions." 


FIG.  32. — SECTION  OF  LIVER  FROM  A  CASE  OF  ECLAMPSIA  SHOWING  EXTREME  CLOUDY 
SWELLING  OF  CELLS,  ALMOST  "MOSAIC"  IN  APPEARANCE,  OTHERWISE  SIMILAR 
TO  FIG.  31. 

TECHNIC  OF  GLYCEMIA  CURVE  ESTIMATES 

Five  samples  of  blood  are  usually  taken  for  sugar  determina- 
tion. The  first,  or  control,  sample  is  taken  with  the  same  needle 
through  which  the  sugar  is  presently  to  be  injected.  Immediately 
after  the  blood  has  been  obtained,  the  syringe  is  disconnected  and 
the  sugar  solution  tube  attached  to  the  needle.  The  time  taken 
to  complete  the  injection  should  be  as  near  thirty  minutes  as  pos- 


TREATMENT 


*43 


sible.  Five  minutes  after  the  injection  is  completed,  Blood  2  is 
taken,  then  thirty  minutes  later  Blood  3,  and  at  one  and  two  hours 
after  Blood  3,  Bloods  4  and  5  are  obtained.  Blood  I  serves  as  a 
control,  Blood  2  represents  the  peak  of  the  blood-sugar  after 
injection,  Blood  3  shows  the  reduction  in  blood-sugar  thirty  min- 
utes after  Blood  2,  and  Bloods  4  and  5  show  whether  or  not  the 
blood-sugar  has  returned  to  the  level  of  Blood  I  during  this  allot- 


FIG.  33. — SECTION  OF  LIVER  FROM  A  CASE  OF  ACUTE  YELLOW  ATROPHY  IN  EARLY 
PREGNANCY,  SHOWING  SWOLLEN,  TURBID  CELLS,  OTHERWISE  FAIRLY  NORMAL. 
Slight  increase  of  connective  tissue  in  the  periportal  spaces  and  round-cell  infiltra- 
tion. Some  cells  contain  fat  globules,  others  coloring  pigment.  Many  cells  con- 
tain double  nuclei  indicating  an  active  proliferating  process.  There  is  no  evidence 
of  necrosis  (Titus). 

ted  interval.  Bloods  2  and  3  are  considered  the  most  important, 
as  they  indicate  the  greatest  amount  of  reduction  in  blood-sugar 
accomplished  by  the  liver  and  tissues  in  thirty  minutes. 

Sugar  in  the  blood  should  be  determined  by  the  Folin-Wu  and 
the  modified  Folin-Wu  procedures. 

The  results  of  a  series  of  cases  studied  by  Titus  and  Givens 
are  given  in  the  accompanying  table. 


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146  TOXEMIAS  OF   PREGNANCY 

In  Group  i  a  number  of  full-term  pregnant  women,  otherwise 
normal,  are  considered.  The  age  limits  are  seventeen  to  thirty- 
six,  the  number  of  pregnancies  one  to  nine.  The  blood-pressures 
are  normal,  and  the  urinary  findings  are  hardly  significant  with 
the  possible  exception  of  Case  5.  To  each  of  these  individuals  25 
grams  of  glucose  were  given  intravenously,  and  with  the  one 
exception  of  patient  i,  who  had  had  breakfast,  all  the  blood-sugars 
before  injection  were  within  the  normal  range. 

The  second  blood-sugars  are  interesting.  The  blood  was 
taken  five  minutes  after  the  injection  was  completed  in  order  that 
sufficient  time  should  have  elapsed  to  insure  a  thorough  mixing 
of  the  sugar  with  the  blood.  The  lowest  blood-sugar  is  171  milli- 
grams per  hundred  cubic  centimeters  of  blood  and  the  highest 
308,  yet  all  patients  received  the  same  amount  of  glucose.  Thirty 
minutes  later  the  corresponding  figures  were  225  and  98.  Un- 
doubtedly the  size  of  the  individual,  the  size  and  activity  of  the 
liver,  and  the  activity  of  the  muscular  tissues  account  to  some 
degree  for  the  variations  in  the  second  blood.  In  the  case  of 
Blood  3  the  reduction  from  the  level  of  Blood  2  must  be  ascribed 
mainly  to  the  liver  because,  of  all  the  factors  mentioned  above,  it 
is  the  variant  of  significance.  In  other  words,  the  reduction  of  a 
blood-sugar  from  0.308  to  0.225  per  cent  in  thirty  minutes  is 
undoubtedly  due  to  the  activity  of  the  liver  cells  in  converting  the 
sugar  into  glycogen  and  storing  it  as  such.  It  has  been  suggested 
that  our  hypothesis  regarding  evidence  for  the  storage  capacity 
of  the  liver  may  not  be  entirely  valid  because  of  another  factor 
which  must  be  considered.  If  it  may  be  assumed  that  there  is  no 
loss  in  injected  sugar  by  way  of  the  kidneys  in  these  experiments, 
one  must  still  think  of  the  possibility  that  there  may  be  a  decrease 
in  the  capacity  of  the  organism  to  utilize  or  destroy  sugar,  as  well 
as  a  diminution  in  the  ability  of  the  liver  to  store  glycogen.  It  is 
conceivable  that  the  former  circumstance  might  lead  to  a  con- 
tinued hyperglycemia;  but  it  would  seem  that  its  influence  on 
these  readings  would  be  slight,  indeed,  as  compared  to  the  broad 
limits  of  variation  which  we  know  to  be  possible  in  the  liver.  Loss 
of  sugar  by  the  kidneys  is  of  little  or  no  significance,  especially  in 
the  presence  of  such  complete  breakage  in  kidney  function  as 
usually  occurs  in  eclampsia. 

The  difference  between  blood-sugars  2  and  3  falls  within  cer- 
tain limits  for  the  group  of  normal  individuals,  the  figures  being 


TREATMENT  147 

from  68  to  106,  to  be  exact.  If  there  is  any  marked  disturbance 
of  the  glycogen  forming  and  storage  function  of  the  liver,  these 
figures  should  be  altered  thereby,  and  we  have  found  such  to  be 
the  case  in  eclampsia.  It  seems  reasonable  to  assume,  from  data 
reported  by  others  as  well  as  from  a  study  of  the  liver  sections  in 
the  fatal  cases,  that  this  alteration  is  due  to  a  pathologic  condition 
of  the  liver. 

Blood  2,  or  the  height  of  the  blood-sugar  five  minutes  after  the 
injection  is  completed,  varies  not  only  because  of  the  factors 
hitherto  mentioned,  but  also  to  a  slight  degree  on  account  of  the 
amount  injected,  if  that  be  very  large.  If  the  same  amount  of 
sugar  were  given  in  each  case,  one  might  then  be  inclined  to 
interpret  a  high  blood-sugar  for  Blood  2  as  indicative  of  liver 
disturbance,  provided  the  tendency  to  remain  high  was  still  evi- 
dent in  Blood  3.  At  present  we  have  no  suggestion  to  offer 
regarding  the  level  of  Blood  2  because  an  inspection  of  the  table 
shows  several  interesting  facts  difficult  to  explain.  For  example, 
the  patients  2  and  6  of  the  normal  group  each  received  25  grams 
of  sugar,  yet  the  blood-sugar  2  of  the  former  was  250,  and  of  the 
latter  171.  The»same  peculiar  variance  will  be  seen  in  some  of  the 
pathologic  cases. 

Among  the  cases  noted,  the  figure  which  seems  to  be  an  index 
of  the  activity  of  the  liver  which,  in  consequence,  may  be  of  prog- 
nostic significance  is,  according  to  the  authors,  the  difference 
between  the  blood-sugars  2  and  3. 

For  the  normally  pregnant  women  as  well  as  for  the  patho- 
logic cases  in  which  the  patients  recovered,  the  limits  of  these 
figures  have  been  49  and  127.  Whenever  the  difference  has  been 
less  than  50  we  have  considered  the  patient's  condition  grave,  and 
40  or  less  as  practically  hopeless.  For  example,  patient  20,  with 
a  difference  of  36  milligrams  between  the  blood-sugars  2  and  3, 
died;  case  23  was  also  fatal,  the  results  of  the  first  injection  being 
suggestive  of  a  grave  condition.  For  therapeutic  reasons  this 
patient  was  given  a  second  injection  and,  when  a  difference  of 
only  36  milligrams  was  found,  the  case  was  considered  hopeless. 
Patients  26  and  28  did  not  show  a  significant  difference  between 
the  blood-sugars  2  and  3,  nor  did  patient  18,  who  died  with  hyper- 
emesis.  The  possible  explanation  of  this  is  that  they  each  showed 
temporary  clinical  improvement  from  the  injection  of  glucose,  a 


148  TOXEMIAS   OF   PREGNANCY 

fact  confirmed  later  by  the  microscopic  examination  of  sections 
of  their  livers.  These  sections  indicate  that  there  was  consider- 
able regeneration  of  the  liver  tissue,  since  the  microscope  does 
not  disclose  the  characteristic  lesions  of  pernicious  vomiting  in 
case  1 8,  or  of  eclampsia  in  the  other  two. 

It  is  evident  from  this  important  recent  work  that  an  imme- 
diate clinical  improvement  results  in  individual  cases  as  well  as  a 
general  lowering  of  the  mortality  rate.  Chorea,  preeclamptic 
toxemia  and  fulminating  toxemias  with  separation  of  the  placenta 
also  showed  favorable  results.  It  is  very  probable,.as  demonstrated  by 
the  authors'  observations,  that  the  rate  of  absorption  and  storage 
of  the  injected  sugar  is  an  index  of  the  condition  of.  the  liver,  so 
that,  if  the  process  can  be  graphically  noted,  a  prognosis  based 
on  such  estimations  is  of  value.  The  slower  the  rate  of  storage 
the  more  we  may  assume  that  there  is  an  actual  and  extensive 
liver  necrosis  with  loss  of  function  and  that  as  this  improves  an 
amelioration  of  the  patient's  symptoms  and  final  favorable  out- 
come of  the  case  may  be  expected. 

SUMMARY 

In  attempting  a  final  summary  of  the  treatment  of  the  tox- 
emias of  pregnancy,  one  is  impressed  by  the  fact  that  through  the 
medium  of  better  prophylaxis  the  incidence  of  these  disorders  of 
pregnancy  is  gradually  diminishing  and  while  a  large  number 
of  cases  is  still  met  with,  the  prognosis,  as  a  general  rule,  is  greatly 
improved.  A.  recognition  of  the  underlying  etiological  factors  in 
the  individual  case  in  so  far  as  they  can  be  determined,  must  con- 
tinue to  be  the  guide  in  the  treatment.  The  laboratory  and  clin- 
ical findings  should  always  be  carefully  weighed  in  their  relation 
to  each  other,  so  that  no  undue  importance  is  attached  to  any  one 
feature  of  the  case  in  determining  whether  the  individual  preg- 
nancy can  be  allowed  to  continue  in  the  presence  of  the  disturb- 
ances of  the  early  months  or  whether  a  change  from  conservative 
to  radical  treatment  is  demanded  in  the  toxemia  of  the  later 
months.  The  ingenuity  of  the  medical  attendant  may  often  be 
taxed  in  dealing  with  a  case  of  hyperemesis  and  the  psychic  ele- 
ment must  be  carefully  considered,  yet  I  firmly  believe  that  con- 


TREATMENT  149 

servative  treatment  is  often  carried  too  far  and  the  emptying  of 
the  uterus  is  delayed  too  long  in  cases  which  are  undoubtedly 
toxic  and  are  irreparably  damaged  by  the  delay.  On  the  other 
hand,  the  often  sudden  and  alarming  symptoms  associated  with 
the  later  toxemias  develop  a  fear  or  even  a  panic  in  the  attending 
physician  that  seems  only  satisfied  by  a  radical  procedure  carried 
out  at  the  expense  of  irreparable  damage,  and  possibly  of  life 
itself. 

Experience  during  recent  years-  has  shown  that  reasonable 
conservatism  has  met  with  good  results  and  repeated  collections 
of  institutional,  statistics  have  demonstrated  that  the  avoidance 
of  shock  in  the  handling  of  the  cases  has  brought  about  remark- 
able reductions  in  morbidity  and  mortality.  But  there  is  still 
much  to  be  done  and  no  branch  of  obstetrics  requires  greater 
thought  and  attention  on  the  part  of  those  seriously  minded  to 
further  improve  the  situation. 


LITERATURE 

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BRODHEAD,   G.   L.      Is   Cesarean   Section  Justifiable   in   Eclampsia? 

N.  Y.  State  Journ.  Med.,  1918,  October. 
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CULBERTSON.     Surg.,  Gyn.  and  Obst.,  1917,  15,  222. 
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i  So  TOXEMIAS  OF  PREGNANCY 

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GUGGISBERG.    Centralbl.  f.  Gynak.,  Leipz.,  1913,  Mch.  15. 

KINGSTON,  C.  A.  F.  Necessity  for  the  Reduction  of  Blood-pressure 
in  Eclampsia.  Proc.  Roy.  Soc.  Med.,  Lond.,  1921,  14,  240. 

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med.  Wchnschr.,  1912,  Aug.  13. 
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i9!3>  37,  i- 

LYNCH,  F.  W.  Treatment  of  the  Severe  Vomiting  of  Early  Preg- 
nancy. Journ.  A.  M.  A.,  1919,  73,  488. 

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MCPHERSON,  Ross.  Conservative  Treatment  of  Eclampsia.  N.  Y. 
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PARKE,  W.  E.  Treatment  of  Eclampsia  by  Cesarean  Section.  Amer. 
Journ.  Obst.,  1918,  77,  948. 


TREATMENT  151 

PETERSON,  REUBEN.    Amer.  Journ.  Obst,  1911,  64,  307.    Ibid.,  1914, 

69,  582. 
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gynec.  et  d'obstet,  1906,  3. 
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Toxemia  of  Pregnancy.     Surg.,  Gyn.  and  Obst,  1912,  15. 
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No.  20. 

REBAUDI.    Gaz.  d.  osp.  Milano,  1909,  Sept.  21. 
REIFFERSCHEID,  K.  Ueber  die  Anwendung  von  Euphyllin  zur  Hebung 

der  Diurese  bei  der   Eklampsie.     Centralbl.    f.   Gynak.,   Leipz., 

1914,  July  25. 

RISSMANN.     Centralbl.  f.  Gynak.,  Leipz.,  1913,  Feb.  8. 
RISSMANN,   P.     Neue  Wege  der  Eklampsiebehandlung.     Ztschr.    f. 

Geburtsh.  u.  Gynak.,  Stuttg.,  1916,  78,  2. 
RONGY.    N.  Y.  State  Journ.  Med.,  1914,  Jan. 
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1919,  i. 
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laktische    Behandlung    der    Eklampsie    und    die    dabeierzielten 

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Tr.  Lond.  Obst.  Soc.,  No.  126,  1904,  46. 
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152  TOXEMIAS  OF  PREGNANCY 

WARD.     Stirg.,  Gyn.  and  Obst.,  1909,  Dec. 

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WINTER,  G.    Ueber  die  Prinzipien  der  Eklampsiebehandlung.    Ztschr. 

f.  Geburtsh.  u.  Gynak.,  Stuttg.,  1916,  78. 
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ZWEIFEL,  P.     Ueber  die  Behandlung  der  Eklampsie.     Monatschr.  f. 

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CHAPTER  V 

URINARY  CONDITIONS  ASSOCIATED  WITH  THE  TOXEMIAS  OF 

PREGNANCY 

BY  FREDERIC  E.  SONDERN,  M.D.,  NEW  YORK 

Ammonia  coefficient  —  Amino-acids  —  Acidosis  —  Starvation  —  Bile  pigment — Urine 
analysis  with  special  reference  to  the  diagnosis  of  toxemia  of  pregnancy — 
Volume  —  Solids  —  Urea  —  Chlorids  —  Indican — Albumin  and  casts — Nitrogen- 
partition —  Acidosis  —  Urobilin  and  bile  pigment  —  Differential  diagnosis  — 
Toxemias  of  pregnancy — Neurosis — Stasis  and  renal  hyperemia — Nephritis. 

The  desirability  of  a  periodic  routine  examination  of  urine  in 
cases  of  pregnancy  has  long  been  an  established  custom  and  the 
need  has  been  made  even  more  apparent  by  the  inclusion  of 
various  additional  clinical  symptoms  under  the  designation  of  tox- 
emia of  pregnancy.  While  the  chemical  blood  examination  has 
added  much  to  our  diagnostic  and  prognostic  knowledge  in  these 
cases,  it  has  not  replaced  the  more  simple  methods  of  urine  analy- 
sis in  the  search  for  indications  of  toxemia  as  well  as  in  the  early 
differential  diagnosis.  Before  considering  in  detail  the  signifi- 
cance of  abnormal  changes  in  the  urine  in  pregnancy,  a  brief  his- 
torical survey  of  the  diagnostic  procedures  in  toxemia  may  be  of 
interest. 

It  has  long  been  a  popular  belief  that  the  urine  of  pregnant 
women  suffering  from  hyperemesis,  eclampsia  and  other  abnor- 
mal symptoms  is  extraordinarily  toxic  to  animals,  but  the  more 
recent  efforts  to  prove  this  theory  by  proper  biologic  tests  tend  to 
create  some  doubt  in  this  respect.  Thus,  Zinsser's  claim  that  he 
has  demonstrated  Pfeiffer's  conclusion  that  a  disintegration  of 
albumoids  causes  anaphylaxis  in  hyperemesis  and  eclampsia,  does 
not  seem  true  in  the  light  of  more  detailed  investigation.  The 
whole  subject  of  the  toxicity  of  the  urine  in  pregnancy  has  been 
reviewed  by  Esch  in  connection  with  his  research  work  and  his 
conclusion  is  that  relatively  little  of  practical  clinical  value  has 
been  determined  in  this  way. 


i54  TOXEMIAS  OF  PREGNANCY 

The  vigorous  and  persistent  search  to  isolate  a  causative  toxic 
substance  was  really  not  undertaken  until  the  clinical  entity  of 
toxemia  of  pregnancy  was  established.  The  studies  of  James 
Young  are  a  notable  example,  although  the  search  for  a 
toxin  in  the  urine  has  remained  fruitless  to  date  and  the  research 
work  which  has  been  done,  while  in  no  sense  conclusive,  suggests 
that  the  urine  is  probably  not  the  carrier  of  the  toxin  itself. 

Soon  after  this  correlation  of  the  symptoms  of  toxemia  of 
pregnancy  as  a  clinical  entity,  the  altered  chemical  composition  of 
the  urine  in  these  cases  was  studied,  but  practically  from  the 
beginning  the  changes  were  considered  a  consequence  of  the 
toxemia,  and  in  no  sense  the  cause.  The  description  of  the  urin- 
ary changes  was  much  too  technical  for  the  average  clinician  of 
that  day,  and,  being  largely  the  result  of  the  work  of  the  biological 
chemist,  the  lack  of  proper  emphasis  that  this  altered  body  chem- 
istry was  the  result  and  not  the  cause  of  the  toxemia  led  to  con- 
fusion in  the  minds  of  many.  Every  now  and  then  articles  still 
appear  ascribing  these  anatomical  changes  in  cases  of  toxemia  of 
pregnancy  to  the  abnormal  conditions  found  in  the  urine;  for 
example,  to  the  acidosis,  with  complete  disregard  of  the  fact  that 
at  least  equally  severe  faults  of  the  same  kind  are  found  in  the 
urine  in  cases  of  diabetes  and  in  cyclic  vomiting  of  children  with- 
out the  presence  of  the  pathological  lesions  associated  with  tox- 
emia of  pregnancy. 

Ammonia  Coefficient. — The  accurate  differentiation  of  tox- 
emia of  pregnancy  from  cases  in  which  similar  symptoms  were 
due  to  other  conditions,  notably  nephritis,  was  formerly  more 
difficult  than  it  is  to-day,  and  pathognomonic  signs  in  the  urine 
were  eagerly  looked  for.  It  soon  became  apparent  that  an  abnor- 
mal nitrogen-partition  in  the  urine  was  the  most  pronounced 
feature,  and  particularly  the  increase  in  the  relative  amounts  of 
ammonia  and  amino-acids.  J.  Whitridge  Williams,  in  1907, 
directed  particular  attention  to  the  ammonia  coefficient — the 
amount  of  ammonia  nitrogen  compared  with  the  amount  of  total 
nitrogen  in  the  urine.  He  not  only  believed  that  the  relative 
increase  in  ammonia  was  in  direct  ratio  to  the  severity  of  the  tox- 
emia, but  that  in  this  way  it  would  be  possible  to  estimate 
accurately  the  value  of  the  treatment  instituted  to  relieve  the  con- 
dition and  also  to  decide  how  far  a  patient  might  be  allowed  to  go 
before  interference  with  pregnancy  was  justified.  In  the  enthu- 


URINARY  CONDITIONS  155 

siasm  of  having  at  last  found  a  practical  method  to  deal  with  a 
difficult  decision,  he  established  the  rule  that  an  increasing  am- 
monia nitrogen  of  10  per  cent,  or  more,  of  the  total  nitrogen  justi- 
fies interference  with  the  pregnancy.  Wider  experience  soon 
established  a  more  conservative  policy  which  Williams  was 
among  the  first  to  adopt,  but  the  fact  remains  that  the  ammonia 
coefficient  is  still  one  of  the  potent  factors  in  determining  just 
what  Williams  originally  claimed — an  index  to  the  severity  of  the 
toxemia  as  well  as  an  index  to  the  point  beyond  which  it  is  not 
Safe  to  allow  the  pregnancy  to  go. 

Amino-acids. — The  advocates  of  the  amino-acid  determination 
or  rest-nitrogen  determination  as  guides  to  the  severity  of  the 
toxemia  soon  lost  ground,  particularly  on  account  of  the  more 
elaborate  technical  procedures  involved,  and  eventually  these 
methods  were  completely  superseded  by  the  ammonia  coefficient 
determinations. 

Acidosis. — The  almost  constant  presence  of  acetone  and  aceto- 
acetic  acid  in  the  urine  in  cases  of  toxemia  of  pregnancy  was  be- 
lieved to  offer  another  means  of  judging  of  the  severity  of  the  con- 
dition. As  the  degree  of  acidosis  evident  in  the  urine  in  this  way 
is,  however,  not  necessarily  a  true  index  of  the  reduced  alkalinity 
of  the  blood,  the  determination  of  the  amount  of  acetone  and 
aceto-acetic  acid  in  the  urine  became  less  important  and  served  as 
corroborative  data  only.  The  determination  of  acetone  and  aceto- 
acetic  acid  in  the  blood  and  of  the  carbon  dioxid  combining  power 
of  the  blood  plasma  now  offers  accurate  means  of  estimating  the 
degree  of  the  existing  acidosis. 

Starvation. — In  cases  of  hyperemesis,  or  other  symptoms  of 
toxemia  of  pregnancy,  there  are  often  considerable  periods  dur- 
ing which  the  patient  receives  or  absorbs  little  or  no  food,  and 
the  effect  of  this  starvation  on  the  ammonia  coefficient  as  well  as 
on  the  existing  degree  of  acidosis  is  a  most  important  factor,  if 
these  evidences  are  to  be  considered  in  estimating  the  severity  of 
the  toxemia.  This  does  not  mean  that  these  aids  in  diagnosis  are 
to  be  disregarded,  or  that  their  value  becomes  nominal  for  this 
reason,  but  it  does  mean  that  the  possible  effect  of  starvation  must 
be  taken  into  consideration  when  these  determinations  are  used 
for  diagnostic  purposes. 

Bile  Pigment. — Owing  to  the  serious  import  of  the  hepatic 
necrosis  which  occurs  in  toxemia  of  pregnancy,  a  careful  watch 


156  TOXEMIAS  OF  PREGNANCY 

for  bile  pigment  in  the  urine  has  been  advised.  Although  delicate 
tests  for  bile  pigment  are  used,  the  evidence  of  jaundice  is  usually 
apparent  clinically  before  the  pigment  can  be  demonstrated  in  the 
urine.  An  excess  of  urobilin  can,  however,  be  found  in  the  urine 
before  bile  pigment  is  demonstrated  or  evidences  of  jaundice  are 
observed. 


URINE    ANALYSIS    WITH    SPECIAL    REFERENCE    TO 
THE  DIAGNOSIS  OF  TOXEMIA  OF  PREGNANCY 

Volume. — The  daily  amount  of  urine  voided  in  pregnancy 
(from  900  cubic  centimeters  to  1,500  cubic  centimeters)  does  not 
vary  essentially  from  that  in  the  nonpregnant  state.  The  changes 
ordinarily  noted  in  functional  or  organic  renal  disorders  are  the 
same;  consequently,  pronounced  variations  from  the  normal  have 
the  same  significance.  Neurotic  polyuria  is  perhaps  more  com- 
mon in  pregnancy;  and,  when  it  occurs,  justifies  greater  care  in 
differential  diagnosis  than  at  other  times.  Frequency  of  micturi- 
tion must  not  be  interpreted  as  evidence  of  increase  in  volume. 

Solids. — The  normal  limits  in  the  amount  of  solids  excreted  in 
the  urine  are  sufficiently  wide  to  include  what  slight  changes 
occur  in  normal  pregnancy.  Since  the  advent  of  blood  chemistry, 
which  determines  accurately  the  presence  or 'absence  of  nitrogen 
or  other  retention  products,  the  amount  of  urinary  solids  is  rela- 
tively of  no  importance  except  perhaps  to  indicate  the  desirability 
of  a  chemical  blood  examination. 

Urea. — The  normal  minimal  daily  excretion  of  urea  in  preg- 
nancy is  about  16  grams,  but  there  is  usually  a  somewhat  reduced 
excretion  immediately  after  parturition.  Now  and  again  cases 
are  met  with  in  which  this  reduced  excretion  is  abnormally  pro- 
nounced and  is  as  low  as  10,  8,  6,  or  even  4  grams,  without  other 
abnormal  signs  in  the  urine  or  any  adverse  clinical  symptoms. 
This  occurrence  has  always  been  the  cause  of  anxiety  and  can 
now  be  avoided  by  determining  the  absence  of  nitrogen  retention 
in  the  blood. 

Chlorids. — The  significance  of  chlorid  retention  in  pregnancy 
has  been  emphasized  chiefly  by  the  German  writers,  but  the 
determination  of  the  amount  of  chlorids  excreted  in  the  urine  is 
not  used  generally  as  a  diagnostic  aid,  as  it  is  replaced  in  a  way 


URINARY   CONDITIONS  157 

by  definite  clinical  signs  in  the  differential  diagnosis  concerned. 
Normally  about  10  grams  are  excreted  in  twenty-four  hours, 
which  amount  is  subject  to  considerable  fluctuation  caused  by  the 
diet.  In  a  consideration  of  the  subject  of  urine  analysis  in  preg- 
nancy it  would  be  impossible  to  discuss  the  significance  of  chlorid 
briefly,  but  the  question  is  an  involved  one  and  has,  or  is  usually 
considered  to  have,  little,  if  any,  relationship  to  the  toxemia  of 
pregnancy.  Zinsser,  however,  attaches  the  greatest  importance 
to  chlorid  retention  in  eclampsia  and  obtains  most  important  diag- 
nostic and  prognostic  information  from  his  chlorid  estimations. 

Indican. — An  excess  of  indican  in  the  urine  is  usually  referred 
to  abnormal  fermentation  or  putrefaction  changes  in  the  intes- 
tinal tract.  Such  an  occurrence  is  undesirable  in  pregnancy  and 
the  indications  for  correction  of  these  alterations  are  obvious. 
Accurate  quantitative  determinations  are  laborious  and  unneces- 
sary, the  usual  tests  being  quite  sufficient  to  determine  the  pres- 
ence of  an  excess  which  has  clinical  significance.  It  is  a  well- 
established  observation  that  toxemia  of  pregnancy  is  very  often 
associated  with  an  indicanuria,  and  in  a  large  number  of  cases 
the  records  indicate  that  a  constant  excess  of  indican  had  been 
present  in  the  urine  of  these  patients  even  before  pregnancy. 
Without  the  effort  or  the  ability  to  prove  an  association  between 
intestinal  toxemia  and  the  toxemia  of  pregnancy,  practical  experi- 
ence has  demonstrated  at  least  coincident  occurrences  of  this  con- 
dition in  many  cases.  For  this  reason  careful  attention  to  the 
elimination  of  intestinal  toxemia  is  advised  as  a  prophylactic 
measure. 

Albumin  and  Casts. — The  frequency  of  albuminuria  in  preg- 
nancy has  long  been  recognized,  and  it  is  generally  understood 
that  about  50  per  cent  of  pregnant  women  show  albumin  in  the 
urine  at  some  time  during  the  period  of  gestation.  This,  of 
course,  includes  slight  traces  of  albumin  which  are  demonstrated 
on  careful  analysis  of  filtered  specimens.  It  is  also  an  established 
fact  that  the  relative  amounts  of  albumin  in  the  daily  amount  are 
not  guides  either  to  the  nature  or  the  severity  of  the  existing 
cause.  The  presence  of  albumin  without  the  presence  of  casts,  or 
of  larger  amounts  of  albumin  with  very  few  hyaline  casts,  are 
more  apt  to  be  due  to  a  functional  disorder  of  the  kidney  in  preg- 
nancy than  in  the  non-pregnant  state,  while  a  true  nephritis  of 
one  or  other  of  the  types  will  present  the  usual  composite  picture 


158  TOXEMIAS  OF  PREGNANCY 

of  the  respective  lesion.  The  amount  of  albumin  found  may  vary 
from  a  slight  trace  to  10  or  more  grams  per  liter  by  weight. 
Whenever  the  presence  of  albumin  is  demonstrated  it  becomes 
an  imperative  duty  to  determine  the  cause  so  far  as  this  is  possible 
in  order  that  proper  measures  be  instituted.  Many  women  are 
made  miserable,  and  many  babies  are  handicapped,  by  the 
assumption  that  any  albuminuria  indicates  the  presence  of  a 
nephritis. 

There  is  nothing  characteristic  about  the  albuminuria  in  tox- 
emia of  pregnancy.  Ordinarily  traces  of  small  amounts  of  albu- 
min are  present  without  casts  or  with  perhaps  an  occasional 
hyaline  cast  coincident  with  the  slight  or  the  more  severe  symp- 
toms of  toxemia.  Only  a  short  time  before,  or  at  the  time  of,  an 
eclamptic  seizure,  the  urine  may  suddenly  present  every  charac- 
teristic of  a  severe  acute  nephritis  with  one  notable  exception, 
namely,  the  signs  often  completely  disappear  from  the  urine  in  an 
incredibly  short  period  after  the  cessation  of  the  eclamptic  attack, 
an  observation  never  made  in  acute  nephritis  due  to  any  other 
cause. 

Nitrogen-partition. — The  important  features  in  the  faults 
found  in  the  nitrogen-partition  of  the  urine  in  cases  of  toxemia  of 
pregnancy  are  the  decrease  in  the  relative 'amount  of  urea  nitro- 
gen with  an  increase  in  the  relative  amount  of  ammonia  nitrogen, 
amino-acid  nitrogen  and  rest  nitrogen.  From  a  practical  clinical 
standpoint  it  is  essential  to  reduce  the  technical  procedure  to  a 
minimum  in  order  to  make  the  method  as  simple  and  as  rapid  as 
possible,  so  long  as  it  renders  all  the  information  which  the 
method  is  capable  of  furnishing.  This  is  accomplished  by  the 
estimation  of  total  nitrogen,  urea  nitrogen  and  ammonia  nitrogen, 
and  calculating  the  percentage  of  the  total  nitrogen  the  two  latter 
figures  represents.  This  determination  can  be  made  by  any  of 
the  approved  methods.  The  urea  nitrogen  cannot  be  estimated 
by  the  hypobromite  method,  as  it  is  not  sufficiently  accurate  at 
any  time,  and  is  particularly  faulty  when  there  is  an  increase  of 
ammonia  nitrogen.  In  normal  urine  the  amount  of  total  nitrogen 
is  about  8  grams  in  twenty-four  hours;  the  urea  nitrogen  about 
6.5  grams,  or  85  per  cent  of  the  total  nitrogen;  and  the  ammonia 
nitrogen  about  0.3  gram,  or  3.5  per  cent  of  the  total  nitrogen. 
In  cases  of  toxemia  of  pregnancy,  as  stated  before  there  is  a 
decrease  in  the  urea  nitrogen  from  85  per  cent  of  the  total  nitro- 


URINARY   CONDITIONS  159 

gen  to  70,  60,  50  per  cent,  or  even  less;  and  an  increase  in  the 
ammonia  nitrogen  from  3.5  per  cent  of  the  total  nitrogen  to  5,  10, 
20,  50  per  cent,  or  more.  In  estimating  the  significance  of  this 
relative  increase  in  the  amount  of  ammonia  nitrogen  in  cases  of 
toxemia  of  pregnancy,  a  gradually  ascending  increase  with  increasing 
evidences  of  an  acidosis,  although  the  patient  has  been  under  suit- 
able treatment,  is  much  more  unfavorable  than  a  single  very  high 
percentage  which  can  often  be  reduced  to  the  normal  by  an  enema 
containing  a  sufficient  amount  of  glucose.  The  probable  influence 
of  starvation  must  not  be  forgotten  at  any  time,  and  the  effect 
of  the  increasing  retention  of  food  should  be  reflected  in  a  cor- 
responding decrease  in  the  ammonia  nitrogen  percentage  if  this  is 
an  important  factor. 

Acidosis. — Smaller  or  larger  quantities  of  acetone  and  of 
aceto-acetic  acid  are  usually  present  in  the  urine  in  cases  of  tox- 
emia of  pregnancy.  Were  these  quantities  only  approximately 
indicative  of  the  amounts  in  the  blood,  a  quantitative  estimate 
would  serve  a  very  useful  purpose,  but  as  this  is  not  the  case,  the 
usual  tests  which  indicate  their  absence,  or  presence,  in  small, 
moderate,  or  large  amount  are  quite  sufficient.  These  simple 
observations  in  addition  to  the  other  tests  made,  serve  a  useful 
purpose  in  estimating  the  severity  of  the  toxemia,  and  offer  a 
good  indication  for  the  need  of  determining  the  carbon  dioxid 
combining  power  of  the  plasma,  and  the  quantitative  estimation 
of  the  acetone  bodies  in  the  blood.  Starvation  has,  if  anything, 
a  greater  effect  on  acidosis  than  on  the  ammonia  coefficient,  and 
this  must  be  borne  constantly  in  mind  when  interpreting  the 
results  of  these  examinations.  Lactose  is  found  in  the  urine  in 
pregnancy  in  a  relatively  large  number  of  cases,  and  it  is  some- 
times not  differentiated  from  glucose,  but  as  there  may  be  a 
coincident  acidosis  of  toxemia,  the  possibility  of  a  wrong  diag- 
nosis of  diabetes  due  to  faulty  observation  is  apparent. 

Urobilin  and  Bile  Pigment. — The  occurrence  of  jaundice  in 
toxemia  of  pregnancy  is  one  of  the  later  and  more  serious  signs, 
and  the  appearance  of  bile  pigment  in  the  urine  is  a  symptom 
watched  for  with  anxiety  in  these  cases.  The  urine,  generally 
small  in  amount  and  concentrated  in  character,  is  usually  highly 
colored  and  the  positive  demonstration  of  bile  pigment  is  not  a 
simple  procedure.  In  fact,  the  clinician  is  usually  able  satisfac- 
torily to  demonstrate  evidences  of  jaundice  before  bile  pigment 


160  TOXEMIAS  OF   PREGNANCY 

is  positively  identified  in  the  urine.  The  relatively  early  recog- 
nition of  an  excess  of  urobilin  is  a  common  experience,  but  it  is 
often  difficult  to  decide  whether  the  apparent  excess  is  due  to 
mere  concentration  or  is  actually  a  sign  of  hepatic,  functional  or 
other  disorders.  At  all  events,  the  significance  of  an  excess  of 
urobilin  and  the  presence  of  bile  pigment  should  be  kept  in  mind; 
and,  finally,  it  must  not  be  forgotten  that  simple  jaundice  due  to 
duodenal  catarrh  can  also  occur  in  pregnancy  with  no  relation 
whatever  to  a  true  toxemia. 

DIFFERENTIAL   DIAGNOSIS 

Toxemia  of  Pregnancy. — In  hyperemesis  associated  with  preg- 
nancy there  is  a  decrease  in  the  daily  amount  of  urine  (400  cubic 
centimeters  to  800  cubic  centimeters  being  common  figures)  ;  an 
increase  in  specific  gravity  with  other  evidences  of  concentration; 
generally  a  tract  of  albumin  without  the  presence  of  casts;  and 
a  decrease  in  the  daily  amount  of  urea  due  to  the  restricted  intake 
of  food,  and  the  changes  in  the  nitrogen-partition.  If  the  am- 
monia coefficient  and  the  presence  of  evidences  of  an  acidosis  in 
the  urine  have  been  determined  from  time  to  time,  gradually 
increasing  amounts  of  acetone  and  aceto-acetic  acid  will  be  noted. 
If,  however,  a  single  estimation  of  the  ammonia  coefficient  is 
made  at  this  time,  it  is  possible  that  an  alarming  figure  may  be 
obtained.  The  institution  of  efficient  treatment  incidentally  will 
result  in  a  decided  improvement  in  these  diagnostic  signs  of 
toxemia. 

Under  these  circumstances  the  continuance  at  regular  inter- 
vals of  the  observations  described  above  is  all  that  is  necessary  to 
confirm  the  clinical  signs.  The  frequency  of  the  examinations 
naturally  will  be  guided  by  the  clinical  symptoms,  on  the  one 
hand,  and  the  laboratory  findings,  on  the  other.  While  a  slight 
or  moderate  toxemia  continues,  the  ammonia  coefficient  will  prob- 
ably fluctuate  between  5  per  cent  and  8  per  cent  with  occasional 
evidences  of  a  mild  acidosis  due  wholly,  or  in  part,  to  the 
restricted  food  intake.  If  at  any  time  the  symptoms  are  out  of 
proportion  to  the  laboratory  findings,  additional  determinations 
are  urgently  advised.  Severe  headaches,  ocular  signs  or  cardiac 
disturbances  with,  or  without,  abnormally  low  total  nitrogen  or 
urea  excretion  should  prompt  a  chemical  blood  examination  to 


URINARY  CONDITIONS  161 

exclude  a  nitrogen  retention.  Clinical  symptoms  with  the  least 
indication  of  acidosis  should  indicate  determination  of  the  carbon 
dioxid  combining  power  of  the  plasma  determination  and  the 
estimation  of  the  acetone  bodies  if  necessary.  On  the  other  hand, 
if  the  urine  examinations  show  evidences  of  increasing  disturb- 
ances, even  though  the  clinical  condition  is  relatively  satisfactory, 
and  particularly  if  the  ammonia  coefficient  continues  to  increase,  a 
sharp  lookout  should  be  kept  for  an  excess  of  urobilin,  bile  pig- 
ment and  evidences  of  nephritis.  The  study  of  a  considerable 
number  of  these  cases  demonstrates  that  the  decision  as  to  how 
long  a  pregnancy  should  be  allowed  to  continue  under  these 
circumstances  does  not  depend  on  any  one  determination,  or  even 
on  any  group  of  determinations.  The  fact  remains,  however,  that 
these  aids  are  essential  in  reaching  a  conclusion,  although  perhaps 
more  so  in  one  case  and  much  less  so  in  another. 

The  condition  just  described  may  result  in  eclampsia.  The 
development  may  or  may  not  be  preceded,  but  is  invariably 
accompanied,  by  all  the  evidences  of  an  acute  nephritis  in  the 
urine.  There  is  usually  a  longer  or  shorter  period  of  complete 
anuria,  followed  by  a  very  scanty  excretion  of  highly  colored  urine 
containing  a  large  amount  of  albumin  and  a  considerable  ad- 
mixture of  blood.  Usually  there  are  also  vast  numbers  of  all 
kinds  of  casts,  chiefly  epithelial  and  granular,  although  for  a  short 
period  at  the  very  beginning  no  casts  at  all  may  be  found.  This 
urine  picture  continues  during  the  eclamptic  period.  If  the  con- 
vulsions and  the  toxemia  end  in  the  emptying  of  the  uterus,  which 
is  often,  but  not  always,  the  case,  it  is  almost  incredible  how 
rapidly  the  abnormal  features  may  disappear  from  the  urine.  It 
is  not  an  unusual  experience  to  receive  a  perfectly  normal  speci- 
men of  urine  from  a  case  of  this  kind  six  hours  after  the  uterus 
has  been  emptied,  thus  terminating  a  most  violent  attack.  It  is 
in  this  respect  that  these  cases  differ  so  noticeably  from  the  cases 
of  uremia  in  pregnancy  with  convulsions  in  which  the  kidney 
recovers,  if  at  all,  in  the  usual  slow  manner  noted  in  a  similar  con- 
dition in  the  nonpregnant.  If  the  urine  is  examined  for  the  first 
time  during  the  convulsive  attack  it  presents  no  evidences  which 
will  aid  in  the  differential  diagnosis  between  a  toxic  eclampsia  and 
nephritic  uremic  convulsions  in  pregnancy. 

Neurosis. — In  women  of  neurotic  temperament  a  condition 
simulating  true  hyperemesis  is  sometimes  observed.  In  most 


162  TOXEMIAS  OF  PREGNANCY 

instances  the  loss  of  food  is  more  imaginary  than  real,  and  the 
urine  shows  none  of  the  evidences  of  toxemia  or  even  the  slightest 
sign  of  acidosis  due  to  starvation.  If,  however,  the  vomiting  does 
interfere  with  nutrition,  acetone  bodies  may  appear  in  the  urine 
and  there  may  be  a  moderate  increase  in  the  ammonia  coefficient, 
but  the  figures  are  never  alarming  and  usually  promptly  return  to 
the  normal  after  efficient  treatment.  A  paroxysmal  neurotic  poly- 
uria  is  not  uncommon  in  these  cases  and  the  decreased  excretion 
of  solids  is  usually  relative  only.  Even  if  associated  with  a  tem- 
porary acidosis  the  picture  scarcely  ever  simulates  a  true  toxemia 
and  a  subsequent  examination  makes  differentiation  a  simple 
matter. 

Stasis  and  Renal  Hyperemia. — Occasionally  cases  are  met 
with  in  which  stasis  due  to  pressure  and  consequent  renal  hyper- 
emia  gives  rise  to  albuminuria  varying  in  severity  and  with  no 
constant  accompanying  evidences  in  the  urine.  The  amount  of 
urine  may  be  large  or  small,  and  the  albumin  varies  from  a  slight 
trace  to  a  considerable  amount,  usually  without  the  presence  of 
casts.  The  daily  amount  of  solids  is  normal  and  there  are  no 
evidences  of  toxemia,  unless  by  chance  this  is  an  associated  con- 
dition, no  instance  of  which  is  recalled.  The  positive  differential 
diagnosis  is  difficult  for  the  very  reason  that  positive  evidences 
are  lacking,  and  it  must,  therefore,  rest  on  the  absence  of  both  the 
clinical  and  the  laboratory  evidences  of  an  actual  renal  lesion. 

Nephritis. — Pregnancy,  without  doubt,  occasions  a  consider- 
able additional  strain  on  renal  function  and  the  presence  of  an 
organic  lesion  of  the  kidney  thus  becomes  an  important  question 
in  safeguarding  the  pregnant  woman.  The  subject  of  nephritis 
in  pregnancy  remains  an  involved  one,  and  is  further  complicated 
by  a  certain  relationship  between  toxemia  of  pregnancy  and  faulty 
renal  function,  if  not  an  actual  renal  lesion.  For  the  purpose  of 
simplifying  the  diagnosis  there  is  a  constant  effort  to  separate 
toxemia  of  pregnancy  from  disordered  renal  function  and  actual 
kidney  involvement,  or  at  most  to  consider  the  former  a  cause  of 
the  latter,  but  the  fact  remains  that  convincing  proof  of  actual  dis- 
association  is  still  lacking. 

ACUTE. — Acute  nephritis,  as  an  intercurrent  complication  in  preg- 
nancy, due  to  any  one  of  the  usual  causes,  runs  a  course  much  the 
same  as  in  the  non-pregnant  state,  except  that,  everything  else 
being  equal,  the  prognosis  is  not  quite  so  favorable.  The  urine 


URINARY  CONDITIONS  163 

picture  may  be  exactly  that  noted  in  toxic  eclampsia  or  in  acute 
exacerbation  of  a  chronic  nephritis,  and,  while  differentiation  at 
the  moment  may  be  impossible,  comparison  with  the  previous 
records  will  at  once  permit  the  proper  classification.  The  sub- 
sequent course  of  the  disease  is  also  characteristically  different  in 
all  respects. 

CHRONIC  INTERSTITIAL. — Chronic  interstitial  nephritis  is  unques- 
tionably rare  in  women  during  the  child-bearing  period.  It  does 
occur,  however,  and,  when  present,  may  show  no  clinical  symp- 
toms and  such  slight  signs  in  the  urine  that  its  existence  may  be 
completely  overlooked.  The  fact  that  a  nephritis  of  this  type,  of 
such  severity  as  not  to  allow  the  completion  of  pregnancy,  and  may 
be  present,  with  but  a  faint  trace  of  albumin  and  a  few  hyaline 
casts  in  the  urine,  is  the  very  reason  wrhy  these  evidences  found  at 
any  time  should  justify  a  painstaking  clinical  and  laboratory 
investigation  to  determine  their  cause.  It  is  in  these  cases  par- 
ticularly, or  in  cases  in  which  this  condition  is  suspected,  that  the 
determination  of  the  presence  or  the  absence  of  nitrogen  reten- 
tion in  the  blood  has  its  greatest  merit.  These  are  the  cases  in 
which  sudden  acute  uremic  convulsions  which  so  closely  resemble 
a  toxic  eclampsia,  may  occur,  that  the  urine  examination  records 
and  the  slower  recovery  in  uremia  patients,  if  they  survive,  offer 
the  only  means  of  differentiation. 

CHRONIC  PARENCHYMATOUS. — This  form  of  nephritis,  more  or 
less  quiescent,  is  the  type  of  Bright's  disease  most  frequently 
encountered  in  pregnancy.  While  it  is  possible  for  a  nephritis  to 
develop  during  pregnancy,  it  is  much  more  probable  that  the 
lesion  was  contracted  during  an  infectious  disease  in  childhood 
and  remained  quiescent  until  greater  functional  demands  were 
made  on  the  kidney  in  the  pregnancy.  This  type  of  nephritis 
is  never  overlooked  in  a  properly  made  urine  analysis,  as  easily 
demonstrated  amounts  of  albumin,  pus  cells  and  casts  are  always 
found  even  in  the  quiescent  stage  of  a  but  slightly  developed 
lesion.  While  a  parenchymatous  nephritis  may  allow  the  com- 
pletion of  a  pregnancy,  its  presence  is  always  the  cause  of  much 
anxiety  and  demands  most  careful  management  even  in  the  mild 
cases.  As  there  is  no  pronounced  nitrogen  retention  in  this  type, 
blood  chemistry  does  not  offer  the  helpful  diagnostic  and  prog- 
nostic information  thus  obtained  in  cases  of  interstitial  nephritis. 
Uremic  convulsions  may,  however,  occur  most  unexpectedly,  and 


1 64  TOXEMIAS  OF  PREGNANCY 

then  the  urine  suddenly  assumes  all  the  characteristics  of  an  acute 
nephritis.  Now  and  again  a  chronic  parenchymatous  nephritis  is 
associated  with  a  true  toxemia  of  pregnancy,  and  this  combination 
may  offer  a  most  difficult  diagnostic  and  prognostic  problem — 
one  which  will  tax  the  ingenuity  of  the  most  astute  clinician. 


LITERATURE 

ALLEN.    Journ.  A.  M.  A.,  1920,  74,  652. 

ALLEN,  STILLMAN  AND  FITZ.  Monographs  of  the  Rockefeller  Insti- 
tute for  Medical  Research,  No.  n,  New  York,  1919. 

BAUMANN,  HANSMAN,  DAVIS  AND  STEVENS.  Arch.  Int.  Med.,  1919, 
24,  70. 

CALDWELL  AND  LYLE.  Am.  Journ.  Obst.,  1921,  2,  17. 

CHERRY  AND  KILLIAN.     Unpublished  observations. 

EMGE.    Am.  Journ.  Obst,  1918,  77.    Ibid.,  1916,  74. 

ESCH.    Arch.  f.  Gynak,  No.  2,  1912. 

EWING.    Am.  Journ.  Obst.  and  Dis.  Worn.,  1905,  51,  145. 

EWING  AND  WOLF.    Am.  Journ.  Obst.,  1907,  55,  289. 

FOLIN.    Am.  Journ.  Physiol.,  1905,  13,  84. 

HASSELBACH  AND  GAMMELTOFT.     Biochem.  Ztschr.,   1915,  68,  207. 

JOSLIN.    The  Treatment  of  Diabetes.     Philadelphia,  1920. 

KAST  AND  WARDELL.    Arch.  Int.  Med.,  1918,  22,  581. 

KILLIAN.     Proc.  Soc.  Exper.  Biol.  and  Med.,  1917,  15,  17. 

KILLIAN  AND  SHERWIN.    Am.  Journ.  Obst,  1921,  2,  6. 

LOSEE  AND  VAN  SLYKE.    Am.  Journ.  Med.  Soc.,  1917,  53,  94. 

MARRIOTT.    Journ.  A.  M.  A.,  1916,  66,  1594. 

MARRIOTT  AND  ROWLAND.    Arch.  Int.  Med.,  1916,  18,  708. 

MORRIS.    Bull.  Johns  Hopkins  Hosp.,  1917,  28,  140. 

MOSENTHAL  AND  HlLLER.      JoUm.  Urol.,   1917,    I,  75- 

MYERS.    Practical  Chemical  Analysis  of  Blood.    St.  Louis,  1920. 
MYERS  AND  FINE.    Chemical  Composition  of  the  Blood  in  Health  and 

Disease.     New  York,  1915. 
MEYERS  AND  FINE.     Journ.  Biol.  Chem.,  1919,  37,  239.     Ibid.  1915, 

21,  377.    Ibid.,  1913,  16,  169.    Ibid.,  1913,  14,  39. 
MEYERS  AND  KILLIAN.    Amer.  Journ.  Med.  Sc.,  1919,  97,  674. 
MEYERS  AND  KILLIAN.    Journ.  Biol.  Chem.,  1917,  29,  179. 
MEYERS  AND  SHORT.    Journ.  Biol.  Chem.,  1920,  44,  47. 
PALMER  AND  VAN  SLYKE.    Journ.  Biol.  Chem.,  1917,  32,  499. 


URINARY  CONDITIONS  165 

PLOSS.     Bull.  Johns  Hopkins  Hosp.,  1917,  28,  137. 

SELLARDS.     The  Principles  of  Acidosis  and  Clinical  Methods  for  Its 

Study.    Cambridge,  Mass.,  1917. 

SLEMOXS  AND  BOGERT.    Journ.  Biol.  Chem.,  1917,  32,  63. 
SLEMONS  AND  MORRIS.     Bull.  Johns  Hopkins  Hosp.,  1916,  27,  343. 
TILESTON  AND  COMFORT.    Arch.  Int.  Med.,  1914,  14,  620. 
UNDERBILL  AND  RAND.    Arch.  Int.  Med.,  1910,  5,  61. 
VAN  SLYKE.    Journ.  Biol.  Chem.,  1917,  30,  347. 
VAN  SLYKE  AND  STADIE.    Arch.  Int.  Med.,  1920,  25,  693. 
WHITE.    Lancet,  Lond.,  1920,  2,  1248. 
YOUNG,  J.    Obst.  Tr.,  Edinburgh,  1913,  39. 
ZINSSER.    Centralbl.  f.  Gynak.,  Leipz.,  April  5,  1913.    Also  Ztschr.  f. 

Geburtsh.  u.  Gynak.,  Stuttg.,  1912. 
ZWEIFEL.    Mimchen.  Med.  Wchnschr.,  1906,  53,  297. 


CHAPTER  VI 

SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD  IN  THE 
TOXEMIAS  OF  PREGNANCY 

BY  JOHN  A.  KILLIAN,  PH.D.,  NEW  YORK 

Chemical  analysis — Nonprotein  nitrogen — Urea  nitrogen — Rest-nitrogen — Uric  acid 
— Creatinin — Chlorids — Alkali  reserve — Carbon  dioxid,  how  determined — Blood 
changes  in — Nephritic  toxemias — Blood  changes — Acute  yellow  atrophy  of  the 
liver — Blood  changes — Hyperemesis — Blood  changes — Carbon  dioxid  combining 
power,  decrease  of — Pre-eclampsias  and  eclampsias — Blood  changes — High 
nonprotein  nitrogen  —  Urea  and  rest-nitrogen  —  Uric  acid  concentration  — 
Creatinin  and  chlorids  —  Hyperglycemia^ —  Nonprotein  nitrogen  distribution  — 
Umbilical  vein  and  artery — Cerebrospinal  fluid — Summary. 

Chemical  Analysis. — The  introduction  of  accurate  and  rapid 
methods  for  the  chemical  analysis  of  blood,  largely  through  the 
work  of  Folin,  Benedict,  Van  Slyke  and  Myers,  has  given  a  new 
impetus  to  biochemical  investigation  within  the  past  ten  years. 
The  application  of  these  methods  to  the  study  of  chemical  changes 
in  the  blood  in  various  pathological  conditions  has  yielded  infor- 
mation of  immense  practical  value  in  the  diagnosis,  prognosis  and 
treatment  of  metabolic  and  constitutional  diseases.  Although  in 
this  chapter  our  object  is  to  e.mphasize  only  those  points  in  the 
chemical  analysis  of  the  blood  which  may  serve  as  a  guide  in  the 
diagnosis  and  treatment  of  the  toxemias  of  pregnancy,  it  is  essen- 
tial at  the  outset  to  discuss  briefly  the  composition  of  normal 
blood  and  the  variations  associated  with  the  more  common  meta- 
bolic disorders.  For  practical  purposes  an  analysis  of  the  blood 
should  include  a  determination  of  the  nonprotein  and  urea  nitro- 
gen, uric  acid,  creatinin,  the  total  chlorids  (as  NaCl),  sugar,  and 
the  carbon  dioxid  combining  power.  In  some  instances  a  knowl- 
edge of  the  diastatic  activity  and  the  cholesterol  content  of  the 
blood  is  of  great  value.  For  a  description  of  the  technic  employed 
in  these  analyses  it  will  suffice  to  refer  to  the  work  of  Myers. 

166 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE   BLOOD         167 

Nonprotein  Nitrogen  in. — The  nonprotein  nitrogen  consti- 
tutes about  i  per  cent  of  the  total  nitrogen  of  the  blood:  varia- 
tions in  the  protein  nitrogen  have  no  direct  bearing  upon  the  con- 
ditions which  we  are  considering  in  this  discussion.  It  will  be 
evident  from  Table  I  that  100  cubic  centimeters  of  normal  blood 
contain  from  25  to  30  milligrams  of  nonprotein  N,  and  from  12 
to  15  milligrams  of  urea  nitrogen.  The  nitrogen,  in  the  urea 
molecule  is  the  chief  component  of  the  nonprotein  nitrogen. 
Mosenthal  and  Hiller  have  pointed  out  that  a  selective  action  of 
the  normal  kidney  maintains  the  urea  nitrogen  at  a  level  of  50  per 
cent,  or  slightly  less,  of  the  total  nonprotein  nitrogen,  but,  an 
impairment  of  kidney  function,  even  of  a  slight  degree,  may  result 
in  an  increase  in  the  percentage  of  the  urea  nitrogen.  In  ad- 
vanced cases  of  renal  involvement,  as  Myers  has  shown,  there  is 
a  marked  increase  in  the  nonprotein  and  the  urea  nitrogen,  but 
the  urea  nitrogen  constitutes  from  75  to  85  per  cent  of  the  non- 
protein  nitrogen.  The  urea  is  largely  synthetized  from  the  am- 
monia produced  in  the  deaminization  of  the  amino-acids  resulting 
from  the  protein  digestion.  It  is,  then,  almost  entirely  of  exogen- 
ous origin.  Obviously  the  character  of  the  diet  will  influence  to 
some  extent  the  nonprotein  and  urea  nitrogen  content  of  the 
blood.  The  nitrogen  of  the  food  is  transported,  by  the  blood  to 
the  various  parts  of  the  organism  for  the  repair  of  old,  or  the 
building  of  new,  tissues.  The  waste  nitrogen  is  carried,  directly 
or  indirectly  to  the  kidneys  for  elimination  by  the  same  medium. 
Hence,  after  a  meal  containing  protein,  there  may  be  a  temporary 
elevation  of  the  nonprotein  and  urea  nitrogen  of  the  blood. 
Tileston  and  Comfort  have  reported  in  healthy  subjects  a  rise  in 
the  nonprotein  nitrogen  of  from  2.9  to  8.5  milligrams  and  in  the 
urea  nitrogen  of  about  2.5  milligrams,  two. and  a  half  hours  after 
consuming  a  heavy  meal.  The  relation  of  the  urea  to  the  non- 
protein  nitrogen,  however,  was  not  .disturbed  by  the  intake  of 
food.  It  is  essential,  therefore,  for  a  comparison  of  results,  that 
specimens  of  blood  should  be  drawn  under  conditions  as  nearly 
uniform  as  possible.  The  best  procedure  is  to  obtain  the  blood 
in  the  morning  before  breakfast,  that  is,  after  a  fast  of  from  12  to 
14  hours.  This  will  eliminate  any  changes  in  composition  due  to 
the  recent  ingestion  of  food. 

RETENTION  OF. — The  conditions  in  which  a  retention  of  nonpro- 
tein and  urea  nitrogen  may  occur  are  very  numerous.  A  marked 


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1 68 


SIGNIFICANT  CHEMICAL  CHANGES   IN  THE   BLOOD         169 

accumulation  of  these  products  is  found  not  only  in  the  advanced 
stages  of  nephritis  of  the  interstitial  type,  but  also  in  such  condi- 
tions as  bichlorid  poisoning,  double  polycystic  kidney,  malig- 
nancy, pneumonia,  cardiac  conditions,  syphilis,  and  gastric  and 
duodenal  ulcer.  In  all  of  these  diseases,  however,  the  retention  is 
due  to  renal  complications,  but  as  in  nephritis  when  the  urea 
nitrogen  is  retained,  it  forms  more  than  50  per  cent  of  the  non- 
protein  nitrogen. 

Urea  Nitrogen  in. — Since  the  urea  nitrogen  is  the  chief  com- 
ponent of  the  nonprotein  nitrogen,  and  its  estimation  is  consider- 
ably simpler,  the  determination  of  the  urea  nitrogen  is  generally 
adopted  in  clinical  work  as  a  diagnostic  index  of  kidney  function. 
A  knowledge  of  the  concentration  of  the  nonprotein  nitrogen  of 
the  blood  alone  is  of  no  definite  value,  but  the  relation  of  the 
urea  nitrogen  to  the  nonprotein  nitrogen  is  of  prime  importance 
in  the  toxemias  of  pregnancy. 

Rest-nitrogen  in. — A  subtraction  of  the  nitrogen  contained  in 
the  well-known  nitrogenous  waste  products  from  the  total  non- 
protein  nitrogen  of  the  blood  gives  a  fraction  called  the  rest- 
nitrogen,  which  comprises  the  nitrogen  contained  in  a  series  of 
little-known  compounds.  Among  these  the  amino-acids  are  prob- 
ably the  most  important.  The  amino-acid  nitrogen  of  normal 
blood  ranges  from  4  to  6  milligrams  per  100  cubic  centimeters, 
but  for  a  short  period  following  the  intake  of  proteins  in  the  diet, 
it  may  rise  to  from  6  to  8  milligrams  per  100  cubic  centimeters. 

Distribution  of  Nonprotein  Nitrogen. — A  comparison  in  Table 
II  of  the  relative  distribution  of  the  nonprotein  nitrogen  of  the 
blood  among  its  known  components  emphasizes  several  points  of 
interest.  It  will  be  noted  that  in  health  the  urea  nitrogen  forms 
about  50  per  cent  of  the  nonprotein  nitrogen,  and  the  rest-nitro- 
gen about  46  per  cent.  In  parenchymatous  nephritis  there  is  no 
change  in  this  nitrogen-partition.  Interstitial  nephritis,  however, 
is  characterized  by  a  pronounced  increase  in  the  percentage  of 
nitrogen  as  urea,  and  a  decrease  in  the  rest-nitrogen.  The  blood 
in  eclampsia  forms  a  marked  contrast  to  this.  In  eclampsia  there 
is  a  relative  drop  in  the  urea  nitrogen,  but  a  very  marked  increase 
in  the  rest-nitrogen.  It  will  be  observed  also  that  the  nitrogen  in 
the  uric  acid  forms  a  greater  fraction  of  the  nonprotein  nitrogen 
than  either  in  nephritis  or  gout.  This  marked  increase  in  the  rest- 
nitrogen  of  blood  is  of  diagnostic  value  in  the  toxemias  of  preg- 


TOXEMIAS   OF   PREGNANCY 


nancy.  The  rest-nitrogen,  however,  can  be  determined  only  by 
subtracting  from  the  total  nonprotein  nitrogen,  the  amount  of 
nitrogen  contained  in  the  urea,  the  uric  acid,  and  the  creatinin. 
No  variations  have  been  noted  in  the  concentration  of  amino- 
acids  or  ammonia,  and  for  clinical  purposes  these  factors  need  not 
be  brought  into  consideration.  Hence  in  eclamptic  bloods  it  is 
essential  to  determine  the  nonprotein  nitrogen  in  addition  to  the 
urea,  uric  acid  and  creatinin. 

TABLE  II 

COMPARATIVE  NITROGEN  PARTITION  OF  BLOOD 
In  per  cent  of  total  nonprotein  nitrogen 


Blood 

Uric 
Acid 

N 

Urea 

N 

Creat- 
inin 

N 

Ammo- 
nia 

N 

Rest 

N 

Normal  

2 

^o 

2 

O.  3 

46 

In  gout  and  early  nephritis  

6 

^o 

2 

o.  3 

42 

In  parenchymatou&  nephritis  .... 

2 

55 

2 

0.3 

40 

In  severe  interstitial  nephritis  .  .  . 

2  to  3 

75 

2-5 

0.5 

20 

Eclampsia  

7  .7 

16 

2 

O.  3 

73 

Uric  Acid. — Urea  is  the  nitrogenous  waste  product  of  the 
metabolism  of  simple  proteins,  but  uric  acid  is  derived  from  the 
metabolism  of  a  group  of  conjugated  proteins — the  nucleins.  The 
nucleins  contain  nucleic  acid,  which  is  split  into  its  various  con- 
stituents by  endocellular  enzymes — the  nucleases.  During  this 
autolysis  the  purin  bases  are  liberated  from  the  other  constituents 
of  the  nucleic  acid  molecule.  These  are  then  deamidized  and 
oxidized  by  a  group  of  enzymes  to  the  final  product — uric  acid. 
The  uric  acid  of  the  blood  has  a  twofold  origin.  One  portion 
arises  from  the  disintegration  of  the  nuclein  material  of  the  body 
tissue;  the  other  portion  is  produced  during  the  metabolism  of 
the  nucleins  of  the  diet.  The  source  of  the  uric  acid  then  is  both 
endogenous  and  exogenous.  The  concentration  of  this  product 
in  normal  blood  after  an  average  mixed  diet  is  from  2  to  3  milli- 
grams per  100  cubic  centimeters.  A  restriction  of  the  purin 
intake  will  diminish  the  amount  of  uric  acid  in  the  blood  possibly 
to  i  or  1.4  milligrams,  while  the  ingestion  of  a  diet  rich  in  purin  leads 


SIGNIFICANT   CHEMICAL  CHANGES  IN  THE  BLOOD         171 

to  an  increase  of  the  uric  acid  in  the  blood.  In  gout  the  concen- 
tration of  this  product  may  rise  to  6  milligrams,  whereas  the  other 
nitrogenous  waste  products  remain  at  their  respective  normal 
levels.  The  etiological  factors  producing  this  high  uric  acid  in 
gout  are  not  understood  at  the  present  time. 

RETENTION  OF. — Myers  and  Fine  have  pointed  out  that  the  kidney 
during  excretion  normally  concentrates  the  creatinin  one  hundred 
times,  the  urea  eighty  times,  but  the  uric  acid  only  twenty  times. 
Hence  of  these  nitrogenous  waste  products  the  creatinin  is  the 
easiest  to  eliminate  and  the  uric  acid  the  most  difficult,  with  the 
urea  standing  in  an  intermediate  position.  The  order  of  retention 
of  these  nitrogenous  waste  products,  as  a  result  of  renal  disease, 
will  depend  upon  the  comparative  ease  with  which  the  kidney 
excretes  them.  A  lowering  of  the  permeability  of  the  kidney  in 
the  initial  stages  of  renal  impairment  leads  to  an  accumulation  of 
the  uric  acid  in  the  blood.  This  retention  of  uric  acid  takes  place 
long  before  there  is  any  appreciable  increase  in  the  nonprotein 
and  urea  nitrogen  or  creatinin,  and  it  is  an  earlier  and  more 
reliable  indication  of  an  insufficiency  of  kidney  function  than  a 
proteinuria  or  cylinduria.  Baumann,  Hansman,  Davis  and 
Stevens,  after  a  thorough  study  of  tests  of,  renal  function  in  a 
large  series  of  cases,  have  concluded  that  the  rise  in  the  concentra- 
tion of  uric  acid  in  the  blood  is  the  most  sensitive  index  of  a  failing 
kidney  function  at  our  disposal.  Later,  as  the  involvement  of 
kidney  function  progresses,  the  urea  accumulates  in  the  blood, 
but  in  general  there  is  no  perceptible  rise  in  the  creatinin  concen- 
tration until  the  urea  nitrogen  has  been  doubled  or  more  than 
doubled. 

INCREASE  OF. — From  the  data  presented  in  Table  III  it  is  evident 
that  in  mild  involvement  of  kidney  function  there  is  a  definite 
increase  in  the  uric  acid,  but  the  urea  nitrogen  and  creatinin 
remain  normal.  In  the  moderately  severe  cases  there  is  a  reten- 
tion of  urea  nitrogen  in  addition  to  the  uric  acid.  The  creatinin, 
however,  remains  fairly  normal.  A  severe  nephritis  entails  a  def- 
inite increase  in  the  creatinin  in  addition  to  the  uric  acid  and  urea 
nitrogen.  The  progressive  steps  in  the  involvement  of  the  excre- 
tion of  these  nitrogenous  waste  products  present  a  staircase 
effect. 

Creatinin. — Creatinin  is  the  anhydrid  of  creatin  (methyl  gua- 
nidin  acetic  acid),  the  chief  nonprotein  nitrogenous  constituent  of 


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SIGNIFICANT   CHEMICAL  CHANGES  IN  THE   BLOOD         173 

muscle.  Folin  first  proved  that  the  amount  of  creatinin  excreted 
in  the  urine  of  a  normal  individual  on  a  meat-free  diet  is  inde- 
pendent of  both  the  amount  of  protein  in  the  food  and  of  the  total 
nitrogen  of  the  urine.  The  creatinin,  therefore,  is  not  derived 
from  the  diet,  but  its  source  on  a  meat-free  diet  is  entirely  en- 
dogenous. The  relation  of  the  creatinin  excreted  to  the  creatin 
content  of  the  muscles  has  long  been  a  disputed  question.  The 
evidence  presented  by  Myers  and  Fine  supports  the  view  that  the 
creatinin  is  formed  in  the  muscle  tissue  from  creatin  at  a  very 
constant  rate.  While  all  muscles  have  the  property  of  producing 
creatin  and  converting  it  into  creatinin,  it  is  certain  that  muscular 
work  does  not  increase  creatinin  production.  Creatin  probably  is 
evolved  and  converted  into  creatinin  in  the  formative  metabolism 
of  muscles  rather  than  during  muscular  contractions.  The  cre- 
atinin is  then  a  product  of  the  "wear  and  tear"  of  the  tissues 
rather  than  of  any  special  function. 

Of  all  the  tissues  of  the  body,  the  kidneys  contain  the  greatest 
amount  of  creatinin,  next  in  order  come  the  muscles  and  then 
the  blood.  This  would  indicate  that  after  its  formation  in  the 
muscles  the  creatinin  is  transported  by  the  blood  to  the  kidney 
for  excretion.  Myers  and  Fine  have  found  in  a  case  of  uremia  a 
creatinin  content  of  the  bloqd  slightly  exceeding  that  of  the 
muscles.  For  normal  individuals  the  creatinin  of  the  blood 
amounts  to  from  i  to  2  milligrams  per  100  cubic  centimeters.  The 
fact  that  creatinin  is  entirely  of  endogenous  origin  and  is  readily 
eliminated  by  the  kidneys  renders  it  an  excellent  prognostic  index 
of  renal  function.  In  miscellaneous  pathological  conditions  un- 
complicated by  renal  involvement  values  below  2.5  milligrams  per 
100  cubic  centimeters  are  obtained.  In  syphilis,  some  cardiac  con- 
ditions, and  occasionally  in  fevers  and  advanced  diabetes,  between 
3  and  4  milligrams  are  found.  An  accumulation  of  the  creatinin 
to  3.5  milligrams,  or  more,  indicates  a  severe  disturbance  of  kid- 
ney function.  Myers  and  Killian  have  shown  that  some  cases 
with  creatinin  values  below  4  milligrams  show  improvement,  but 
almost  invariably  a  fatal  termination  from  the  kidney  damage 
results  when  the  creatinin  rises  to  more  than  4  milligrams  per  100 
cubic  centimeters.  A  retention  of  creatinin  to  this  extent  indi- 
cates a  severe  impairment  of  renal  function. 

Chlorids. — The  description  of  a  simplified  technic  for  the 
determination  of  the  chlorids  of  the  blood  by  Myers  and  Short 


I74  TOXEMIAS  OF   PREGNANCY 

has  made  it  possible  to  include  this  estimation  in  our  chemical 
analyses  of  the  blood  for  clinical  purposes.  Some  workers  have 
confined  their  studies  to  the  chlorids  of  the  whole  blood,  and 
others  to  chlorids  of  the  plasma  or  serum.  Normally  the  total 
chlorids  of  the  whole  blood  (determined  as  NaCl)  range  from  0.45 
to  0.50  per  cent,  but  the  chlorids  of  the  plasma  are  about  0.12  per 
cent  higher.  Since  the  tissues  of  the  body  come  into  intimate  con- 
tact with  the  blood  plasma  rather  than  the  whole  blood,  it  is 
logical  to  expect  that  changes  in  the  chlorid  content  of  the  tissues 
would  be  more  significantly  reflected  in  similar  variations  in  blood 
plasma.  However,  on  standing,  or  upon  shaking,  there  is  an 
escape  of  CO2  from  the  blood,  which  produces  a  passage  of 
chlorids  from  the  cells  into  the  plasma.  This  increases  the  chlorid 
content  of  the  plasma  but  does  not  affect  the  chlorids  of  the  whole 
blood.  Hence  determinations  made  upon  the  whole  blood  are 
more  trustworthy  than  those  upon  the  plasma. 

The  excretion  of  chlorids  and  nitrogen  appear  to  be  independ- 
ent functions  on  the  part  of  the  kidneys.  In  nephritis  of  the  inter- 
stitial type  the  excretion  of  nitrogen  is  markedly  impaired,  but 
the  excretion  of  chlorids  is  fairly  normal.  Here  when  high  blood 
chlorids  are  found,  a  restriction  of  the  chlorid  intake  quickly 
restores  them  to  normal.  However,  the  restriction  of  the  chlorid 
intake  must  always  be  gauged  by  the  level  of  the  blood  chlorids. 
In  parenchymatous  nephritis,  on  the  contrary,  the  nitrogen  reten- 
tion is  comparatively  small,  but  there  is  diminished  excretion  of 
chlorids.  This  retention  of  chlorids  is  accompanied  by  an  edema, 
and  the  blood  chlorids  gradually  return  to  normal  with  the  sub- 
sidence of  the  edema.  Allen  has  recently  endeavored  to  establish 
a  causative  relation  between  the  retention  of  chlorids  in  the  plasma 
and  the  development  of  hypertension  simplex,  and  hypertension 
in  renal  disease.  Subsequent  experimental  studies  on  the  part  of 
other  workers  have  failed  to  confirm  Allen's  contention.  Fur- 
thermore, our  studies  on  toxemias  of  pregnancy  have  shown  that 
in  these  conditions  there  is  no  definite  relation  between  the  level 
of  the  blood  chlorids  and  the  hypertension,  but  that  the  appear- 
ance of  the  edema  was  paralleled  by  a  significant  rise  in  the 
chlorids  of  the  whole  blood.  Apparently  a  deficiency  of  chlorid 
excretion  is  a  causative  factor  in  producing  this  edema,  and  a 
limitation  of  the  chlorid  intake,  guided  by  the  level  of  the  blood 
chlorids,  leads  to  a  diminution  of  the  edema.  In  cases  manifesting 


SIGNIFICANT  CHEMICAL  CHANGES   IN  THE  BLOOD        175 

edema,  the  value  of  the  estimation  of  the  blood  chlorids  for  the 
guidance  of  treatment  cannot  be  overemphasized. 

The  sugar  concentration  of  normal  blood  after  a  fast  of  from 
12  to  14  hours  is  0.09  to  0.12  per  cent.  However,  after  a  meal 
rich  in  carbohydrate,  there  may  be  an  appreciable  rise  in  the 
blood-sugar  to  0.13  or  0.14  per  cent.  Blood-sugar  concentrations 
exceeding  0.12  per  cent  are  termed  hyperglycemias,  and  less  than 
0.09  per  cent  hypoglycemias.  Hypoglycemias  are  found  in  con- 
ditions resulting  from  a  hypo-endocrin  function,  for  example, 
myxedema,  cretinism,  Addison's  disease  and  also  in  muscular  dys- 
trophy. Hyperglycemias  are  more  commonly  encountered,  for 
example,  in  diabetes,  nephritis  and  hyperthyroidism.  Myers  and 
Killian  have  shown  that  the  hyperglycemia  in  nephritis,  diabetes 
and  hyperthyroidism  is  dependent  upon  an  increased  diastatic 
activity  of  the  blood.  The  increased  diastatic  activity  in  nephritis 
finds  an  explanation  in  diminished  excretion  of  this  enzyme  in  the 
urine.  The  mechanism  of  the  production  of  the  hyperactivity  of 
the  diastase  in  the  blood  in  diabetes  is  still  an  obscure  point. 
However,  a  hyperfunction  of  the  ductless  glands,  particularly  of 
the  thyroid,  appears  to  result  in  an  increased  diastatic  activity 
and  a  hyperglycemia.  The  author  has  noted  a  parallelism 
between  the  alkali  reserve  and  the  diastatic  activity  of  the  blood. 
An  increase  in  the  alkali  reserves  inhibits  the  diastatic  activity, 
whereas  a  decrease  in  the  alkali  reserve  provokes  an  increased 
activity.  The  hyperglycemias  noted  in  the  toxemia  of  pregnancy 
find  a  possible  explanation  in  the  variations  in  the  diastatic  activ- 
ity of  the  blood. 

Alkali  Reserve. — During  health  the  blood  is  constantly  main- 
tained at  a  slightly  alkaline  reaction  through  the  medium  of  its 
bicarbonates,  phosphates  and  proteins.  These  compounds  con- 
stitute the  alkali  reserve  of  the  blood.  A  diminution  of  this  alkali 
reserve  is  commonly  called  an  acidosis,  although  this  term  is 
somewhat  misleading,  since  the  blood  never  during  life  becomes 
acid  in  reaction.  Acidosis  may  be  produced  either  by  an  abnor- 
mal formation  of  acid  substances,  or  it  may  be  due  to  an  inability 
to  remove  from  the  body  acid  compounds  normally  present  in  the 
blood.  The  kidneys  excrete  an  acid  urine  from  a  fairly  neutral 
blood.  The  acidity  of  the  urine  is  largely  due  to  excess  of  acid 
phosphates  over  alkaline  phosphates.  This  removal  of  acid  phos- 
phates by  the  kidneys  is  one  means  of  maintaining  the  alkali 


176  TOXEMIAS  OF  PREGNANCY 

reserve  of  the  blood.  In  nephritis  the  kidneys  may  lose  the  power 
to  eliminate  these  compounds,  and  this  failure  to  excrete  them 
gives  rise  to  a  predominance  of  the  acid  phosphates  over  the 
alkaline  phosphates,  thus  depleting  the  alkali  reserve  of  the  blood. 
Marriott  and  Rowland  have  demonstrated  an  increase  in  the  inor- 
ganic phosphates  in  the  blood  plasma  in  nephritis  with  acidosis, 
but  no  increase  was  noted  in  nephritis  unaccompanied  by  acidosis. 
The  acidosis  of  nephritis  is  then  due,  not  to  an  abnormal  produc- 
tion of  acid  bodies,  but  rather  to  the  accumulation  of  acid  phos- 
phates which  the  kidneys  fail  to  remove.  It  is  important  to  note 
that  the  acidosis  of  nephritis  is  not  accompanied  by  a  ketosis 
(acetonuria),  and  the  only  reliable  method  of  detecting  or  esti- 
mating this  acidosis  is  by  determining  the  alkali  reserve  of  the 
blood. 

The  defective  oxidation  of  the  fats  in  diabetes  leads  to  the  pro- 
duction of  the  acetone  bodies — acetone,  diacetic  acid  and  |3-oxy- 
butyric  acid.  The  neutralization  of  these  compounds  by  the 
sodium  bicarbonate  of  the  blood  plasma  results  in  the  taking  up  of 
the  sodium  by  the  organic  acids  and  a  liberation  of  the  carbon 
dioxid.  In  this  manner  the  body  is  robbed  of  its  alkali  reserve. 
In  the  eclamptic  toxemias  and  in  pernicious  vomiting  a  very 
marked  decrease  in  the  alkali  reserve  has  been  found.  There  can 
be  no  doubt  that  the  acidosis  in  pernicious  vomiting  is  a  type  of 
starvation  acidosis  due  to  production  of  abnormal  acid  bodies  in 
faulty  metabolism.  In  the  eclamptic  toxemias  the  repeated  tonic 
muscular  contractions  result  in  the  formation  of  such  acid  bodies 
as  lactic  acid  and  acid  phosphates.  There  is  also  the  additional 
acid  production  due  to  the  starvation.  Zweifel  isolated  sarcolactic 
acid  in  considerable  quantities  from  the  maternal  venous  blood 
and  the  blood  of  the  cord.  He  ascribed  the  eclamptic  toxemias 
to  an  acid  intoxication.  Although  it  is  now  definitely  known  that 
the  acidosis  is  the  effect  rather  than  the  cause  of  the  toxemia,  a 
knowledge  of  the  extent  of  this  acidosis  is  of  prime  importance 
from  a  therapeutic  standpoint. 

The  body  is  able  to  handle  quite  large  quantities  of  acids  with- 
out a  drop  in  the  alkali  reserve.  The  increased  carbon  dioxid 
tension  of  the  blood  plasma,  due  to  the  liberation  of  carbon  dioxid 
from  the  bicarbonates  in  the  neutralization  of  the  acids,  incites  an 
increase  of  pulmonary  ventilation.  In  this  manner  the  carbon 
dioxid  is  removed  at  a  rapid  rate.  The  acetone  bodies  are  elim- 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD        177 

inated  in  the  urine  producing  a  ketosis  (acetonuria).  An  abnor- 
mal formation  of  ammonia  takes  place  from  the  amino  groups 
split  off  from  the  amino  acids,  and  this  serves  to  neutralize  a  por- 
tion of  the  organic  acids.  The  increased  production  of  the 
ammonia  is  at  the  expense  of  the  urea.  Finally,  the  proteins  may 
react  as  bases  and  take  up  considerable  quantities  of  the  acids 
without  a  perceptible  change  in  their  reaction.  If  the  acid  bodies 
are  neutralized  and  eliminated  without  producing  a  diminution  of 
the  alkali  reserve  of  the  blood  plasma,  this  condition  is  termed 
a  compensated  acidosis.  However,  when  a  decrease  in  the  alkali 
reserve  follows  the  acid  intoxication,  the  acidosis  is  said  to  be 
uncompensated.  A  compensated  acidosis  is  frequently  noted 
during  the  last  months  of  normal  pregnancy. 

Obviously  the  occurrence  of  acetone  bodies  in  the  urine  indi- 
cates an  abnormal  acid  production,  but  it  tells  us  nothing  concern- 
ing the  extent  of  the  acidosis.  Moreover,  in  nephritic  acidosis 
and  in  the  nephritic  toxemias,  a  ketosis  is  uniformly  absent.  In 
like  manner  no  reliance  can  be  placed  upon  the  amount  of  am- 
monia excreted,  or  the  ammonia  coefficient,  for  these  factors  bear 
no  definite  relation  to  the  decrease  of  the  alkali  reserve  of  the 
blood.  A  determination  of  the  carbon  dioxid  tension  in  the 
alveolar  air  by  the  simple  method  of  Marriott  readily  lends  itself 
to  clinical  work.  When  the  determinations  are  made  with  care, 
the  results  furnish  a  fair  index  of  the  acidosis.  However,  in  cases 
of  increased  pulmonary  ventilation,  a  lowered  tension  of  carbon 
dioxid  in  the  expired  air  will  be  noted,  although  no  uncompen- 
sated acidosis  exists.  The  depletion  of  the  alkali  reserve  of  the 
blood  may  be  roughly  determined  by  the  Sellards  method  of 
alkali  tolerance.  This  procedure  has  been  adopted  by  White  in 
a  study  of  acidosis  associated  with  the  toxemias  of  pregnancy. 
Normally  from  5  to  10  grams  of  sodium  bicarbonate  are  sufficient 
to  render  the  urine  alkaline.  In  acidosis  greater  quantities  of  the 
alkali  are  required,  in  some  cases  as  high  as  100  grams.  Palmer 
and  Van  Slyke  have  found  that  in  many  pathological  cases  the 
urine  did  not  become  alkaline  until  the  plasma  bicarbonate  had 
been  increased  above  that  present  in  normal  individuals.  This 
gives  not  only  an  exaggerated  conception  of  the  acidosis,  but  also 
necessitates  the  administration  of  alkali  in  quantities  sufficient  to 
prove  injurious. 


i78 


TOXEMIAS   OF   PREGNANCY 


Carbon  Dioxid,  How  Determined. — Van  Slyke  has  introduced 
a  comparatively  simple  method  of  determining  the  carbon  dioxid 
combining  of  the  blood  plasma  as  a  measure  of  its  alkali  reserve. 
This  method  has  been  almost  universally  adopted  in  clinical 
laboratories.  For  a  detailed  description  of  the  technic  employed, 
reference  may  be  made  to  Myers'  work  or  to  the  original  paper  of 
Van  Slyke  and  Cullen.  The  procedure  consists  in  measuring  the 
reserve  alkali  by  determining  the  amount  of  carbon  dioxid  it  can 
hold  in  combination,  just  as  in  gastric  analyses  the  acid  concentra- 
tion is  estimated  in  terms  of  the  amount  of  alkali  that  will  com- 
bine with  it.  The  table  below  gives  the  range  of  finding  for 
normal  blood  and  the  principal  stages  of  acidosis. 

TABLE  IV 


Condition  of  Subject 

COa  Combining  Power  of  Plasma, 
c.c.  per  100 

Normal  resting  adult.     Extreme  limits  

77-^3 

Mild  acidosis,  no  visible  symptoms  

^—  4.O 

Severe  acidosis,  symptoms  of  acid  intoxication  . 

Below  31 

Lowest  CO->  observed,  with  recovery  

16 

The  etiological  factors  producing  the  acidosis  may  vary,  but 
the  effect  is  the  same  in  all  cases,  that  is,  a  lowering  of  the  alkali 
reserve  of  the  blood.  Hence  the  carbon-dioxid  combining  power 
of  the  blood  plasma  is  a  reliable  index  of  all  types  of  acidosis. 

NORMAL  PREGNANCY 

Blood  Changes  in. — Studies  on  5  cases  of  normal  pregnancy 
are  presented  in  Table  V.  The  nonprotein  nitrogen  is  at  a  low 
normal  level,  or  slightly  decreased  (21  to  25  milligrams),  and  cor- 
responding to  this  there  is  a  proportionate  diminution  in  the  urea 
nitrogen  (9  to  n  milligrams).  The  relation  of  the  urea  nitrogen 
to  the  nonprotein  nitrogen  furnishes  a  reliable  estimate  of  the 
rest-nitrogen.  In  normal  pregnancy  the  urea  nitrogen  forms 
about  44  per  cent  of  the  nonprotein  nitrogen,  slightly  less  than  in 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE   BLOOD         179 


normal  nonpregnant  cases.  The  figures  for  uric  acid,  creatinin, 
and  chlorids  are  well  within  normal  limits.  With  the  exception 
of  cases  i  and  2,  normal  blood-sugars  have  been  found.  In  these 
cases  slight  hyperglycemias  were  noted.  A  definite  decrease  in 
the  carbon  dioxid  combining  power  of  the  blood  plasma  was 
found  to  be  the  rule  in  the  last  months  of  normal  pregnancy. 
The  maximum  decrease  was  to  39  volumes  per  cent.  This  drop 
in  the  alkali  reserve  was  not  associated  with  a  ketosis,  but  was 
found  to  be  associated  with  mild  symptoms  of  dyspnea  after 
physical  exertion.  It  is  evident  from  these  findings,  and  also 
from  the  works  of  Hasselbach  and  Gammeltoft,  of  Losee  and 
Van  Slyke,  and  of  White  and  Emge  that  a  mild  acidosis  prevails 
during  the  last  months  of  pregnancy. 

TABLE  V 
COMPOSITION  OF  THE  BLOOD  IN  NORMAL  PREGNANCY 


Case 

Age 

Para 

Mos. 
of 
Gest. 

Blood  Analyses 

Non- 
protein 

N 

Urea 

N 

UreaN 

Uric 
Acid 

Creati- 
nin 

Sugar 

Chlo- 
rids 

CO2 

Com- 
bining 
Power 

N-P-N 
Per  cent 

Mg.  per 
100  c.c. 

Mg.  per 
100  c.c. 

Per  cent 

i.  A.  P. 

20 

I 

5 

25 

ii 

42 

2  .O 

2-3 

0-13 

0.48 

2.  N.  C. 

25 

I 

7i 

25 

ii 

45 

2.6 

2.  I 

o.  14 

0.46 

42 

3.  A.  S. 

23 

I 

8  ' 

24 

ii 

47 

2.6 

2-5 

O.  10 

0.48 

49 

4.  E.  Q. 

27 

I 

8 

22 

10 

44 

2-5 

2-4 

O.  II 

0.48 

44 

5.  M.  N. 

33 

III 

8    • 

21 

9 

44 

1.9 

2.0 

O.  IO 

0.48 

39 

NEPHRITIC   TOXEMIAS 

Blood  Changes  in. — The  group  of  nephritic  toxemias  embraces 
those  cases  that  in  their  previous  histories  and  in  many  of  their 
clinical  findings  present  evidence  of  a  preexisting  impairment  of 
kidney  function,  either  acute  or  an  exacerbation  of  a  chronic  con- 
dition. The  renal  insufficiency  is  not  consequent  to  the  toxemia, 
but,  on  the  contrary,  it  may  have  been  a  predisposing  cause 


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euroretinitis.  Convulsions.  Sti 
Died  after  cesarean  section 

euroretinitis.  No  edema.  Delive 
bag.  Improvement  slight 

on  vulsions.  No  edema.  Ctfearean. 
dead 

euroretinitis.  Convulsions.  Slig 
provement  after  cesarean 

euroretinitis.  No  edema.  Convi 
Delivered  by  forceps.  Improvemen 

arked  edema.  No  convulsions, 
improvement  after  cesarean 

arked  edema.  Neuroretinitis.  IN 
vulsions.  Cesarean.  Improved 

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180 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD        181 

toward  the  development  of  the  toxemia.  Seven  cases  are  reported 
in  Table  VI.  The  first,  five  show  a  marked  impairment  of  nitrogen 
elimination.  A  comparison  of  these  findings  with  those  in  Tables 
II  and  III  demonstrates  that  the  changes  observed  in  the  blood 
of  these  cases  are  in  accord  with  the  variations  typical  of  mod- 
erate or  severe  renal  impairment  in  general.  The  nonprotein 
nitrogen  is  greatly  increased  (45  to  189  milligrams),  but  the  char- 
acteristic feature  of  these  cases  is  that  the  urea  nitrogen  consti- 
tutes a  larger  fraction  of  the  nonprotein  nitrogen  than  in  normal 
blood.  Such  is  also  the  case  in  nonpregnant  nephritics.  The 
retention  of  uric  acid  is  quite  marked,  but  there  is  no  very  appre- 
ciable increase  in  the  creatinin  except  in  the  first  2  cases.  Case  I 
died  about  forty-eight  hours  after  delivery.  The  creatinin  here 
rose  to  17.6  milligrams.  All  of  these  patients  were  eclamptics, 
and  not  merely  cases  of  nephritis  complicating  pfegnancy.  It  is 
inconceivable  that  such  an  extreme  damage  to  kidney  function  as 
that  presented  in  Case  I  could  develop  from  a  toxemia  within 
twenty-four  to  forty-eight  hours,  as  Caldwell  and  Lyle  maintain. 
There  must  have  been  some  previous  kidney  damage  which 
favored  the  development  of  the  toxemia.  Following  the  evacua- 
tion of  the  uterus,  there  is  but  little  improvement  in  these  cases 
and  the  chemical  changes  in  the  blood  point  to  a  more  or  less  per- 
manent disturbance  of  kidney  function. 

Another  type  of  toxemia  of  renal  origin  is  represented  by  the 
last  2  cases.  The  urea  and  nonprotein  nitrogen  do  not  vary  from 
the  normal,  but  the  uric  acid  is  definitely  increased  (5.1  to  5.2 
milligrams).  The  chlorid  concentration  of  the  blood  was  found 
to  be  0.52  and  0.55  per  cent.  These  high  blood  chlorids  in  spite 
of  a  salt-free  diet  were  .coincident  with  a  pronounced  general 
anasarca  which  had  been  progressing  for  some  time  previous  to 
the  patient's  admission  to  the  hospital.  The  output  of  urine  was 
scanty  and  it  contained  a  large  amount  of  protein.  These  findings 
indicate  a  definite  impairment  of  chlorid  excretion  with  but  little 
involvement  of  nitrogen.  These  2  cases  at  no  time  had  convul- 
sions, but  they  did  complain  of  pronounced  visual  disturbances 
accompanied  by  nausea  and  headache.  After  emptying  the  uterus 
and  giving  medical  treatment  to  increase  salt  elimination,  the 
subsidence  of  the  edema  was  antedated  by  a  decrease  in  the  blood 
chlorids.  In  this  type  of  case,  the  variations  in  the  blood  chlorids 


182  TOXEMIAS  OF_  PREGNANCY 

are  of  the  greatest  value  from  a  prognostic  and  therapeutic  stand- 
point. 

We  may  now  discuss  the  blood  pictures  in  the  various  types 
of  toxemia  according  to  the  classification  adopted  in  the  section 
on  Etiology. 


ACUTE  YELLOW  ATROPHY  OF  THE  LIVER 

Blood  Changes  in. — In  acute  yellow  atrophy  of  the  liver  there 
is  a  complete,  or  almost  complete,  loss  of  function  of  this  organ, 
with  little  or  no  impairment  of  the  functions  of  other  organs. 
Van  Slyke  and  Stadie  have  reported  fairly  complete  chemical 
studies  upon  the  blood  and  urine  in  a  case  of  acute  yellow  atrophy. 
Of  the  total  nitrogen  excreted  in  the  urine  (twenty-four  hours 
before  death)  about  52  per  cent  was  in  the  form  of  urea,  17  per 
cent  as  ammonia,  and  16  per  cent  as  amino-acids.  The  output 
of  the  urea  nitrogen  was  diminished,  but  both  the  ammonia  and 
amino-acid  nitrogen  were  very  markedly  increased.  The  urea 
nitrogen  of  the  blood  remained  within  normal  limits,  but  the 
amino-acid  nitrogen  was  from  two  to  three  times  the  normal 
figure.  A  decrease  in  the  alkali  reserve  of  the  blood  was  also 
noted.  An  examination  of  the  nitrogen  content  of  the  liver  in 
this  case  demonstrated  an  amino-acid  and  peptid  nitrogen  content 
about  three  times  as  great  as  that  found  in  normal  dogs'  livers. 
These  results  point  to  the  conclusion  that  in  acute  yellow  atrophy 
the  proteins  of  the  liver  are  autolyzed  at  a  rapid  rate  into  peptids 
and  amino-acids.  In  the  normal  human  organism  from  85  to  95 
per  cent  of  the  amino-acid  nitrogen  is  converted  into  urea,  the 
amino-acid  nitrogen  constituting  but  4  to  8  milligrams  per  100 
cubic  centimeters  of  the  blood,  and  but  2  per  cent  of  the  total 
nitrogen  of  the  urine.  However,  in  the  case  studied  by  Van  Slyke 
and  Stadie,  only  60  per  cent  of  the  amino-acid  nitrogen  was  trans- 
formed into  urea,  and  the  amino-acid  nitrogen  of  the  urine  rose  to 
16  per  cent  of  the  total  nitrogen.  Acute  yellow  atrophy,  with  the 
possible  exception  of  fatal  phosphorus  poisoning,  is  the  only  clin- 
ical condition  in  which  abnormal  quantities  of  amino-acids  are 
found  in  the  blood  and  urine. 

One  case  of  acute  yellow  atrophy  has  come  under  the  observa- 
tion of  the  author.  During  the  fifty  hours  of  the  patient's  stay  in 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD         183 

the  hospital  there  was  persistent  nausea  and  vomiting  and  a  pro- 
nounced jaundice.  A  post-mortem  examination  confirmed  the 
diagnosis.  A  specimen  of  blood  was  obtained  about  thirty  hours 
before  death  which  was  found  to  contain  80  milligrams  of  non- 
protein  nitrogen,  27  milligrams  of  urea  nitrogen,  and  14.5  milli- 
grams of  uric  acid.  The  urea  nitrogen  here  forms  33  per  cent  of 
the  nonprotein  nitrogen.  The  amino-acid  nitrogen  was  not  deter- 
mined, but  it  is  evident  that  there  is  a  significant  increase  in  the 
rest-nitrogen.  In  this  case,  the  increase  in  the  urea  nitrogen  and 
of  the  uric  acid  must  be  attributed  to  a  secondary  involvement  of 
kidney  function  as  well  as  to  protein  autolysis.  The  increase  in 
the  rest-nitrogen  observed  in  this  case  is  somewhat  similar  to  that 
found  in  eclampsia ;  however,  the  factors  causing  this  increase  in 
the  nonprotein  nitrogen  appear  to  be  different  in  the  two  con- 
ditions. Despite  the  marked  degenerative  changes  that  occur  in 
the  liver  in  the  toxemias  of  pregnancy,  Losee  and  Van  Slyke  have 
found  no  increase  in  the  amino-acid  nitrogen  of  the  blood  or  urine. 

HYPEREMESIS 

Blood,  Changes  in.— In  Table  VII  are  presented  findings  in 
typical  cases  of  hyperemesis.  The  nonprotein  nitrogen  is  def- 
initely increased  above  the  normal  (34  to  65  milligrams) ;  with 
the  exception  of  case  5,  the  urea  nitrogen  is  normal  or  slightly 
decreased.  It  is  evident  that  since  in  these  cases  the  urea  nitro- 
gen forms  a  low  fraction  of -the  nonprotein  nitrogen  (from  15  to 
31  per  cent)  the  rest-nitrogen  must  be  proportionately  increased. 
In  case  5,  although  there  is  a  moderate  retention  of  urea  nitrogen 
amounting  to  27  milligrams,  it  forms  only  41  per  cent  of  the  non- 
protein  nitrogen.  Here  there  is  a  marked  impairment  of  kidney 
function,  but,  as  in  many  cases  to  be  discussed  later,  this  renal 
impairment  is  secondary  to  the  toxemia.  Cases  of  hyperemesis 
are  characterized  by  an  increase  in  the  nonprotein  nitrogen  with 
an  abnormally  small  fraction  in  the  form  of  urea.  It  will  be  noted 
that  these  patients  also  show  an  increased  uric  acid ;  however,  the 
increase  in  the  concentration  of  this  product  is  not  so  great  as  that 
noted  in  eclampsia.  No  disturbance  of  the  creatinin,  sugar  or 
chlorids  has  been  observed. 

Carbon  Dioxid  Combining  Power,  Decrease  of. — A  decrease 
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SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD         185 

invariably  noted  in  our  cases.  The  figures  reported  range  from 
28  to  46.  Hyperemesis  is  then  associated  with  a  more  or  less 
severe  acidosis.  Emge  has  found  a  carbon  dioxid  combining 
power  of  the  blood  plasma  from  35  to  46  in  the  excessive  vomiting 
of  pregnancy.  In  the  cases  of  pernicious  vomiting  reported  by 
Losee  and  Van  Slyke  there  is  a  decrease  in  the  alkali  reserve  of 
the  blood,  but  it  is  not  greater  than  that  observed  in  normal 
pregnancy.  In  following  the  progress  of  the  toxemia  it  has  been 
noted  that  the  depression  of  the  carbon  dioxid  combining  power 
of  the  blood  follows  the  rise  in  the  nonprotein  nitrogen  and  the 
appearance  of  the  clinical  symptoms  of  the  toxemia.  The  acidosis 
is  not  an  etiological  factor  in  the  production  of  the  hyperemesis, 
but,  on  the  contrary,  appears  to  be  dependent  on  the  severity  and 
duration  of  the  nausea  and  vomiting.  A  somewhat  similar  con- 
clusion has  been  reached  by  Underhill  and  Rand  in  their  studies 
on  the  ammonia  excretion  in  the  urine.  These  authors  have 
pointed  out  that  the  composition  of  the  urine  in  pernicious  vomit- 
ing is  strikingly  similar  to  that  found  in  inanition.  The  acidosis, 
gauged  by  the  ammonia  excretion,  is  promptly  relieved  by  the 
administration  of  carbohydrate  by  mouth  or  by  rectum.  The 
acidosis  of  hyperemesis'appears  to  be  a  type  of  starvation  acidosis. 
Although  this  acidosis  is  the  effect,  rather  than  the  cause,  of  the 
toxemia,  from  a  therapeutic  standpoint  a  knowledge  of  any 
change  in  the  alkali  reserve  of  the  blood  is  of  great  value.  Despite 
the  fact  that  both  Joslin  and  Allen  are  opposed  to  the  extensive 
use  of  sodium  bicarbonate  in  acidosis,  the  administration  of  this 
alkali  has  been  generally  accepted  as  the  most  efficient  means  of 
combating  an  acidosis.  However,  Palmer  and  Van  Slyke  advise 
the  careful  control  of  the  amount  of  the  alkali  used.  These 
authors  have  found  that  for  each  forty-two  pounds  of  body  weight 
0.5  gram  of  sodium  bicarbonate  will  raise  the  carbon  dioxid  com- 
bining power  i  per  cent  by  volume.  The  practical  value  of  a 
knowledge  of  the  carbon  dioxid  combining  power  of  the  blood  can 
well  be  illustrated  by  case  I.  Here  an  evacuation  of  the  uterus  to 
relieve  the  hyperemesis  was  decided  upon,  but  since  anesthesia 
and  operative  procedure  decrease  the  alkali  reserve  of  the  blood, 
it  is  essential  first  to  relieve  the  existing  acidosis.  The  carbon 
dioxid  combining  power  must  be  raised  from  28  to  60,  that  is, 
32  volumes  per  cent.  The  body  weight  was  one  hundred  and  two 
pounds,  that  is  2.4  times  Van  Slyke's  unit  (forty-two  pounds).  The 


1 86  TOXEMIAS  OF  PREGNANCY 

dose  of  sodium  bicarbonate  required  in  this  case  to  restore  the 
normal  alkali  reserve  of  the  blood  was  calculated  as  follows: 
0.5  X  2.4  X  32  =  38.4  grams.  The  sodium  bicarbonate  was  given 
intravenously  in  enough  water  to  make  a  4  per  cent  solution. 
This  amount  of  alkali  is  sufficient  to  replenish  the  alkali  reserve 
of  the  blood,  but  to  maintain  it  within  normal  limits,  bicarbonate 
in  a  2  per  cent  solution  was  administered  by  rectum  after  opera- 
tion until  all  symptoms  of  the  toxemia  had  disappeared. 


PRE-ECLAMPSIAS  AND  ECLAMPSIAS 

Blood  Change  in. — In  Table  VIII  cases  I  and  2  are  pre- 
eclampsias,  the  following  5  cases  are  post-partum  eclampsias,  and 
the  remaining  cases,  are  ante-partum  eclampsias.  Although  the 
term  "hepatic  toxemia"  has  frequently  been  applied  by  some 
clinicians  to  this  type  of  pregnancy  toxemia,  we  have  no  proof 
that  this  condition  is  of  hepatic  origin.  Inspection  of  the  table 
discloses  that  the  nonprotein  nitrogen  is  invariably  above  the  high 
normal  limit,  and  in  some  instances  more  than  double  this  figure. 
The  values  found  range  from  29  to  94  milligrams.  In  the  pre- 
eclampsias  the  increase  in  the  nonprotein  nitrogen  is. not  so  great 
as  in  the  true  eclampsias.  With  the  exception  of  the  last  4  cases, 
the  urea  nitrogen  is  at  the  low  normal  level  or  markedly  de- 
creased; values  from  5  to  14  milligrams  being  obtained.  A 
remarkably  low  percentage  of  the  nonprotein  nitrogen  is  in  the 
form  of  urea.  The  highest  percentage  found  was  38  and  the  low- 
est 15. 

HIGH  NONPROTEIN  NITROGEN. — We  believe  that  the  high  non- 
protein  nitrogen,  of  which  the  urea  nitrogen  forms  a  small  per- 
centage, is  characteristic  of  the  pregnancy  toxemias  of  this  type. 
This  low  ratio  of  the  urea  nitrogen  to  the  nonprotein  nitrogen 
indicates  a  marked  increase  in  the  rest-nitrogen.  The  increase  in 
the  rest-nitrogen  cannot  be  explained  by  a  rise  in  the  amino-acid 
nitrogen.  In  a  series  of  23  cases  of  toxemias  studied  by  Van 
Slyke  and  Losee  the  amino-acid  nitrogen  of  the  urine  did  not 
exceed  3.6  per  cent,  the  maximum  found  in  the  urine  of  normal 
men.  The  blood  of  10  eclamptic  women  gave  figures  for  the 
amino-acid  nitrogen  within  4  to  8  milligrams,  the  normal  estab- 
lished by  Ellis,  Cullen  and  Van  Slyke.  The  high  rest-nitrogen 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD         187 

with  a  normal  amino-acid  nitrogen  characterizes  the  eclamptic 
patient  but  a  high  rest-nitrogen  with  an  increased  amino-acid 
nitrogen  is  found  only  in  acute  yellow  atrophy  of  the  liver. 

UREA  AND  REST-NITROGEN. — The  high  nonprotein  and  the  low 
urea  nitrogen  of  the  blood  in  eclampsia  form  a  significant  contrast 
to  the  findings  for  these  products  in  the  blood  in  nephritic  tox- 
emias. In  nephritic  toxemias  the  nonprotein  nitrogen  is  in- 
creased, but  there  is  proportionately  a  greater  rise  in  the  urea 
nitrogen,  so  that  the  urea  nitrogen  forms  more  than  50  per  cent 
of  the  nonprotein  nitrogen.  It  has  been  our  experience  that  the 
increase  in  the  rest-nitrogen  of  the  blood  in  eclampsia  (judged  by 
the  relation  of  the  urea  to  the  nonprotein  nitrogen)  bears  a  some- 
what definite  relation  to  the  extent  of  the  toxemia.  In  the  pre- 
eclampsias  there  is  a  beginning  increase  in  the  nonprotein  nitro- 
gen, the  ratio  of  the  urea  to  the  nonprotein  nitrogen  being 
slightly  less  than  in  normal  pregnancy.  In  the  eclampsias,  how- 
ever, at  the  height  of  the  toxic  state  the  rise  in  the  nonprotein 
nitrogen  is  very  marked,  and  the  ratio  of  the  urea  nitrogen  to  it 
is  relatively  decreased.  Moreover,  the  toxemia  is  relieved  by 
therapeutic  measures,  and  the  subsidence  of  the  toxemia  is  pre- 
ceded by  a  drop  in  the  nonprotein  nitrogen.  Apparently,  the 
factor  causing  the  toxemia  is  a  component  of  this  increased  rest- 
nitrogen,  but  its  nature  and  origin  are  still  matters  of  speculation. 

URIC  ACID  CONCENTRATION. — The  increase  in  the  concentration 
of  uric  acid  is  very  marked  and,  we  are  convinced,  particularly  sig- 
nificant. It  will  be  noted  that  the  uric  acid  figures  vary  from  3  to 
ii  milligrams.  Slemons  and  Bogert  obtained  normal  figures  for 
uric  acid  in  the  blood  in  uncomplicated  pregnancy,  but  in  pre- 
eclampsia,  eclampsia  and  nephritis  complicating  pregnancy,  values 
from  6  to  9  milligrams  were  obtained.  Caldwell  and  Lyle  have 
reported  an  average  figure  of  6.2  milligrams  for  the  uric  acid  of 
the  blood  in  pregnancy  toxemias  and  eclampsias.  Slemons  and 
Bogert  have  noted  an  increase  in  the  uric  acid  content  of  the  blood 
at  the  end  of  labor,  and  this  increase  was  more  pronounced  in 
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that  the  muscular  contractions  during  labor  might  increase  the 
production  of  endogenous  uric  acid.  In  a  similar  manner  the  con- 
vulsions in  eclampsia  would  give  rise  to  a  high  uric  acid  content 
of  the  blood.  Such,  however,  is  not  the  case.  Uric  acid  is  not 
derived  from  muscular  activity.  It  has  been  noted  by  Killian  and 


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IQO  TOXEMIAS  OF  PREGNANCY 

Sherwin  that  the  increase  in  the  uric  acid  content  of  the  blood  in 
eclampsia  is  accompanied  by  other  evidences  of  renal  impair- 
ment, for  example,  by  proteinuria  and  cylindruria.  There  can  be 
no  question  but  that  this  increase  in  the  concentration  of  uric  acid 
must  be  attributed  to  a  mild  involvement  of  kidney  function  con- 
sequent to  the  toxemia.  A  determination  of  the  uric  acid  of  the 
blood  does  not  help  to  differentiate  the  types  of  pregnancy  tox- 
emias, but  as  an  index  of  an  early  disturbance  of  kidney  function 
its  value  cannot  be  overestimated. 

It  will  be  noted  that  in  the  last  4  cases  the  urea  nitrogen  has 
been  increased  above  tire  upper  normal  level  (18  to  22  milli- 
grams). Kast  and  Wardell  have  concluded  as  a  result  of  careful 
studies  on  the  significance  of  the  concentration  of  the  urea  nitro- 
gen in  the  blood  in  various  conditions,  that  values  of  20  milligrams 
or  more  have  a  pathological  significance.  The  only  factor  capable 
of  producing  an  increase  of  the  urea  nitrogen  of  the  blood  is  dis- 
turbance of  kidney  function.  It  is  indeed  true  that  an  increase 
in  exogenous  protein  metabolism  entails  a  greater  production  of 
urea,  but  with  normal  kidney  function  an  increased  elimination  of 
urea  results  so  that  the  urea  nitrogen  of  the  blood  is  maintained 
within  normal  limits.  The  impairment  of  the  functioning  power 
of  the  kidneys  has  advanced  in  these  last  4  cases  so  far  that  it  not 
only  inhibits  the  excretion  of  uric  acid,  but  also  that  of  the  urea. 
However,  it  is  significant  that  in  these  cases,  although  there  is  a 
retention  of  urea,  the  urea  nitrogen  of  the  blood  continues  to  form 
only  a  small  percentage  of  the  nonprotein  nitrogen.  A  com- 
parison of  these  figures  with  those  for  the  nephritic  toxemias 
demonstrates  that  the  actual  amounts  of  nonprotein  and  urea 
nitrogen  in  themselves  are  of  no  value  in  differentiating  the  types 
of  toxemia,  but  the  ratio  of  the  urea  nitrogen  to  the  nonprotein  is 
characteristic  for  each  type. 

The  statement  of  Ewing  and  Wolf  that  persistent  toxemia 
tends  to  involve  the  kidneys  progressively  is  confirmed  by  the 
observations  on  case  20.  In  the  ante-partum  specimen  of  blood, 
obtained  when  convulsions  lasting  from  three  to  four  minutes  were 
rapidly  succeeding  one  another,  the  nonprotein  nitrogen  was 
found  to  be  64  milligrams,  the  urea  nitrogen  18  milligrams,  the 
uric  acid  7.5  milligrams,  and  the  creatinin  1.7  milligrams,  the  urea 
nitrogen  constituting  only  28  per  cent  of  the  nonprotein  nitrogen. 
The  convulsions  ceased  after  the  evacuation  of  the  uterus,  but 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD        191 

otherwise  there  was  no  improvement.  The  patient  continued  in 
a  semicomatose  state,  general  edema  developed  and  there  was  but 
a  slight  drop  in  the  blood  pressure.  Another  specimen  of  blood 
was  obtained  eight  days  after  parturition  when  the  patient 
appeared  to  be  in  a  critical  condition.  There  were,  however,  no 
convulsions.  At  this  time  the  nonprotein  nitrogen  had  risen  to 
90  milligrams,  the  urea  nitrogen  to  43  milligrams,  the  uric  acid 
had  dropped  to  3.2  milligrams,  but  the  concentration  of  creatinin 
was  increased  to  3.7  milligrams.  It  is  pertinent  to  note  that  in 
this  second  specimen  of  blood  the  urea  nitrogen  forms  a  much 
larger  portion  of  the  nonprotein  nitrogen  than  in  the  ante-partum 
specimen.  At  the  height  of  the  toxemia  the  increase  in  the  rest- 
nitrogen  had  reached  its  maximum.  The  disturbance  of  kidney 
function  which  was  indicated  by  the  increased  uric  acid  in  the  ante- 
partum  blood  had  progressed,  in  spite  of  the  termination  of  the 
pregnancy  to  such  an  extent  that  a  marked  retention  of  urea  and 
a  mild  accumulation  of  creatinin  resulted.  The  order  of  retention 
of  these  nitrogenous  waste  products  in  cases  of  renal  impairment 
consequent  to  the  toxemias  of  pregnancy  is  in  close  accord  with 
that  frequently  described  by  Myers  and  his  coworkers. 

CREATININ  AND  CHLORIDS. — No  variation  from  the  normal  was 
noted  in  the  concentration  of  the  blood  creatinin.  In  some 
instances  there  was  a  definite  increase  in  the-  chlorids  of  the  blood. 
In  cases  3  and  18  the  chlorids  rose  to  0.63  per  cent,  in  12  to 
0.58  per  cent,  and  in  16  to  0.55  per  cent.  This  rise  in  the 
blood  chlorids  was  found  to  be  associated  with  a  more  or  less  pro- 
nounced edema.  No  apparent  relation  between  the  level  of  the 
blood  chlorids  and  the  hypertension  could  be  determined.  In 
case  24  the  blood-pressure  rose  to  210/110,  although  the  chlorids 
were  0.42  *per  cent,  while  in  case  16  the  blood-pressure  was 
164/100,  and  the  chlorids  were  increased  to  0.55  per  cent.  Case 
3  had  a  blood-pressure  of  165/100  and  a  chlorid  concentration  of 
0.63  per  cent.  A  study  of  the  progress  of  the  toxemias  has  dem- 
onstrated that  the  rise  in  the  blood-pressure  appears  almost  as 
early  in  the  course  of  the  toxic  state  as  the  increase  in  the  non- 
protein  nitrogen.  However,  a  change  in  the  concentration  of  the 
chlorids  of  the  blood  appears  late  in  development  of  the  toxemia, 
and  apparently  is  due  to  a  disturbance  of  cardiac  or  renal  func- 
tion. Moreover,  in  case  6  at  the  height  of  the  toxemia  the  blood- 
pressure  was  190/100,  and  the  chlorids  0.46  per  cent.  After  the 


I92  TOXEMIAS  OF  PREGNANCY 

disappearance  of  the  toxemia  the  blood-pressure  had  dropped  to 
100/65,  but  the  chlorids  rose  to  0.50  per  cent.  Allen's  explana- 
tion of  hypertension  is  not  confirmed  by  these  studies  upon  the 
toxemias  of  pregnancy. 

HYPERGLYCEMIA. — A  mild  hyperglycemia  has  been  frequently 
noted  in  eclampsia.  Morris  has  shown  that  a  rise  in  the  blood- 
sugar  is  evident  after  convulsions  in  the  eclamptic  toxemias. 
Since  the  specimens  of  blood  studied  by  us  were  obtained  during 
the  convulsive  period,  the  hyperglycemias  may  be  attributed  to 
this  factor.  In  only  one  instance,  case  20,  was  the  diastatic 
activity  of  the  blood  determined.  Here  a  blood-sugar  of  0.30  per 
cent  with  a  diastatic  activity  of  28  was  found  with  a  carbon  dioxid 
combining  power  of  10.  Two  weeks  later  when  the  recovery  was 
complete,  the  blood-sugar  had  dropped  to  0.12  per  cent,  the 
diastatic  activity  to  16  and  the  carbon  dioxid  combining  power 
had  risen  to  48.  This  patient  gave  no  history  of  diabetes  previous 
to  the  toxemia,  and  since  leaving  the  hospital  there  has  been  no 
evidence  of  a  glycosuria.  Killian  has  shown  that  in  diabetes  a 
decrease  in  the  alkali  reserve  of  the  blood  provokes  an  increased 
diastatic  activity  and  a  corresponding  hyperglycemia,  whereas  a 
rise  in  the  alkali  reserve  inhibits  the  diastatic  activity  with  a  con- 
sequent drop  in  the  blood-sugar.  In  a  similar  manner,  variations 
in  the  diastatic  activity  of  the  blood  may  be  found  to  be  the  cause 
of  the  hyperglycemias  in  eclampsia.  This  point,  however, 
requires  further  corroboration. 

In  the  eclampsias  the  decrease  in  the  carbon  dioxid  combining 
power  (42  to  10  volumes  per  cent)  is  particularly  striking,  indi- 
cating in  most  cases  a  severe  acidosis.  In  this  particular  the  cases 
of  hyperemesis  and  eclampsia  differ  markedly  from  the  nephritic 
toxemias.  As  in  hyperemesis,  this  acidosis  of  eclampsia  is  con- 
sequent to  the  toxemia  and  a  relief  of  the  toxemia  provokes  a 
rise  in  the  alkali  reserve  of  the  blood.  The  findings  in  case  22  are 
of  interest  in  this  connection.  Here,  during  the  eclamptic  period, 
the  carbon  dioxid  combining  power  had  dropped  to  26,  but  in  the 
fatal  nephritis  following  the  toxemia,  the  carbon  dioxid  combin- 
ing power  rose  to  52.  At  this  time,  however,  there  were  no  con- 
vulsions. It  will  be  observed  that  the  acidosis  in  the  eclampsia  is 
much  greater  than  in  hyperemesis  or  in  pre-eclampsia.  Another 
factor  in  addition  to  the  starvation  may  be  the  cause  of  the  acid- 
osis in  eclampsia.  In  general,  it  may  be  said  that  the  greatest 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD         193 

decrease  in  the  carbon  dioxid  combining  power  is  found  in  those 
cases  manifesting  severe  convulsions.  It  is  well-known  that  vio- 
lent and  protracted  muscular  contractions  produce  excessive 
amounts  of  sarcolactic  acid.  Zweifel's  demonstration  of  this  acid 
in  the  maternal  venous  and  cord  blood  after  eclamptic  seizures 
has  already  been  cited.  This  and  other  acid  bodies  may  abstract 
some  of  the  alkali  of  the  body  during  excretion  and  thus  cause  an 
acidosis.  The  fact  that  an  increase  in  the  alkaline  reserve  of  the 
blood  promptly  follows  the  cessation  of  the  convulsions,  as  in 
cases  8,  n,  and  24,  lends  support  to  this  explanation.  From  a 
surgical  standpoint  a  knowledge  of  the  carbon  dioxid  combining 
power  of  the  blood  is  of  prime  importance.  No  patient  should  be 
subjected  to  general  anesthesia  and  operation  until  the  alkali 
reserve  of  the  blood  has  been  brought  up  to  normal.  The  manner 
of  doing  this  has  been  described  under  hyperemesis. 

The  chemical  changes  noted  in  the  blood  in  hyperemesis  are 
analogous  to  those  in  post-partum  eclampsia  and  eclampsia  with 
gravid  uterus.  These  findings  are  of  interest  in  view  of  the  state- 
ment of  Ewing  that  pernicious  vomiting  and  eclampsia  are 
identical  in  nature  and  have  the  same  etiology.  In  both  condi- 
tions a  general  clinical  improvement  appears  to  be  consequent  to 
a  resumption  of  the  normal  composition  of  the  blood.  In  case  n 
the  toxic  symptoms  disappeared  five  days  after  delivery,  and  at 
this  time  the  blood  was  found  to  be  normal.  But  it  was  only  after 
a  period  of  fourteen  days  that  cases  8  and  22  presented  evidence 
of  improvement. 

Nonprotein  Nitrogen  Distribution.  A  study  of  the  nonprotein 
nitrogen  distribution  in  the  fetal  circulation  and  a  comparison 
with  that  in  the  maternal  circulation  has  been  attempted  by  numerous 
workers.  Siemens  and  Morris  have  determined  the  nonprotein 
and  urea  nitrogen  in  the  cord  blood  and  maternal  venous  blood  at 
the  end  of  labor.  In  the  maternal  blood  they  obtained  an  average 
nonprotein  nitrogen  of  25.2  milligrams,  a  urea  nitrogen  of  10.4 
milligrams — 44  per  cent  of  the  nonprotein  nitrogen.  In  the  fetal 
blood  (presumably  the  umbilical  venous  blood)  the  nonprotein 
nitrogen  averaged  24.9  and  the  urea  nitrogen  10.4,  or  45  per  cent 
of  the  nonprotein  nitrogen.  Slemons  and  Bogert  have  made 
simultaneous  determinations  of  the  uric  acid  in  the  maternal 
venous  blood  and  the  blood  of  the  umbilical  vein.  Equivalent 
values  were  found  for  the  uric  acid  in  both  specimens  of  blood. 


I94 


TOXEMIAS  OF  PREGNANCY 


Ploss  has  come  to  similar  conclusions  with  regard  to  the  creatinin. 
Caldwell  and  Lyle  have  found  the  nonprotein  and  urea  nitrogen 
and  creatinin  in  maternal  and  fetal  blood  practically  identical  in 
20  cases  at  the  end  of  labor.  These  authors  do  not  state  whether 
the  fetal  blood  was  arterial  or  venous.  Obviously  from  such 
results  no  conclusions  can  be  drawn  concerning  either  the  func- 
tions of  the  placenta  or  the  origin  of  toxic  factors  in  the  toxemias. 
Umbilical  Vein  and  Artery. — Cherry  and  Killian  have  suc- 
ceeded in  separating  the  blood  of  the  umbilical  vein  from  that  of 
the  umbilical  arteries  and  a  comparison  of  the  nitrogen-partition  in 
these  specimens  with  that  in  maternal  venous  blood  in  normal  and 
toxic  cases  has  brought  to  light  some  points  of  interest.  In  some 
cases  the  nitrogen-partition  of  the  spinal  fluid  has  also  been 
determined. 

TABLE  IX 

A  COMPARISON  or  THE  NONPROTEIN  AND  UREA  NITROGEN  AND  URIC  ACID  OF 
THE  MATERNAL  VENOUS  AND  UMBILICAL  VENOUS  AND  ARTERIAL  BLOOD 
AND  OF  THE  MATERNAL  CEREBROSPINAL  FLUID 


Patient 

Blood  of 

Non- 
protein 

N 

Urea 

N 

UreaN 
Per  Cent 
of 
Non- 
protein 

Uric 
Acid 

Remarks 

Mg.  per 

IOO  C.C. 

Mg.  per  100  c.c. 

A.  B. 

Maternal  vein 

25 

12 

48 

2-3 

Normal 

Umbilical  vein 

21 

II 

51 

2.8 

Umbilical  artery 

33 

IO 

3° 

4-9 

M.H. 

Maternal  vein 

37 

II 

29 

4.2 

Eclampsia 

Umbilical  vein 

42 

13 

30 

3-8 

Umbilical  artery 

53 

9 

17 

7-o 

Maternal  cerebro- 
spinal  fluid 

22 

10 

44 

Trace 

The  umbilical  arteries  are  carrying  blood  from  the  fetus  to  the 
placenta,  and  this  blood  is  actually  venous  in  character.  The 
umbilical  vein  is  transporting  the  purified  or  arterial  blood  from 
the  placenta  to  the  fetus.  In  the  normal  case  in  Table  IX  the 
blood  of  the  umbilical  vein  has  approximately  the  same  com- 
position as  that  of  the  maternal  circulation.  In  this  our  findings 


SIGNIFICANT  CHEMICAL  CHANGES  IN  THE  BLOOD         195 

are  in  accord  with  those  of  Siemens  and  Bogert.  The  blood  of 
the  umbilical  artery  (venous),  however,  shows  a  higher  non- 
protein  nitrogen  and  a  greater  concentration  of  uric  acid.  It  also 
will  be  noted  that  the  ratio  of  the  urea  nitrogen  to  the  nonprotein 
nitrogen  is  much  less  than  that  of  the  umbilical  venous  or  ma- 
ternal blood.  In  the  eclamptic  patient  also,  the  maternal  and 
umbilical  venous  bloods  have  similar  nitrogen-partitions.  How- 
ever, the  umbilical  arterial  blood  forms  a  marked  contrast  to  this. 
Here  there  is  a  marked  increase  in  the  nonprotein  nitrogen,  and 
a  decrease  in  the  urea  nitrogen,  the  urea  nitrogen  forming  only  17 
per  cent  of  the  nonprotein  nitrogen.  The  uric  acid  concentration 
is  nearly  double  that  of  the  umbilical  venous  blood.  It  would 
appear  from  such  results  as  these  that  the  increase  in  the  non- 
protein  nitrogen  in  the  maternal  blood  in  eclampsia  may  be  due 
partly  to  an  absorption  of  nitrogenous  bodies  from  the  fetus. 

Cerebrospinal  Fluid. — The  study  of  the  nitrogen  distribution 
of  the  cerebrospinal  fluid  in  eclampsia  was  undertaken  to  deter- 
mine whether  the  pronounced  disturbance  of  the  central  nervous 
system  are  due  to  a  diffusion  of  the  toxic  element  into  the  spinal 
fluid.  It  will  be  observed  in  the  case  recorded  in  the  table  that  the 
nonprotein  nitrogen  of  the  cerebrospinal  fluid  is  but  60  per  cent 
of  that  of  the  maternal  blood,  but  the  urea  nitrogen  is  about  90 
per  cent.  Hence  in  the  spinal  fluid  the  urea  nitrogen  forms  a 
larger  fraction  of  the  nonprotein  nitrogen  than  in  the  blood.  In 
the  cerebrospinal  fluid  the  amount  of  uric  acid  was  too  small  to 
estimate.  Myers  and  Fine  report  that  in  15  miscellaneous  cases 
showing  varying  degrees  of  nitrogen  retention,  the  concentration 
of  urea  in  the  spinal  fluid  averages  88  per  cent  of  that  of  the  blood, 
and  the  uric  acid  but  5  per  cent.  The  authors  state  that  these 
percentage  differences  represent  the  order  of  solubility  of  the 
compounds  in  water,  and  apparently  also  the  order  of  their  dif- 
fusibility.  The  concentration  of  urea  nitrogen  and  of  the  uric  acid 
in  the  cerebrospinal  fluid  in  eclampsia  is  in  agreement  with  the 
results  of  Myers  and  Fine,  but  there  is  a  marked  difference  in 
the  relative  amounts  of  nonprotein  nitrogen.  This  fact  would 
lead  us  to  believe  that  some  of  the  components  of  the  increased 
nonprotein  nitrogen  of  the  eclamptic  blood  are  less  diffusible  than 
uric  acid,  and  that  the  disturbances  of  the  central  nervous  system 
in  this  toxemia  cannot  be  due  to  the  diffusion  of  the  toxic  element 
into  the  cerebrospinal  fluid. 


i96  TOXEMIAS   OF   PREGNANCY 

Chart  I  (Fig.  i)  presents  graphically  the  average  values  for 
nonprotein  and  urea  nitrogen  and  uric  acid  in  cases  of  normal 
pregnancy,  chronic  nephritis,  nephritic  toxemias,  hyperemesis 
and  eclampsia.  It  is  evident  that  in  nephritic  toxemias  the  rela- 
tion of  the  urea  nitrogen  to  the  nonprotein  is  analogous  to  that 
characteristic  of  chronic  nephritis.  But  in  hyperemesis  and 
eclampsia  the  disturbance  of  this  relation  is  very  striking.  It  will 
also  be  noted  that  the  average  value  for  uric  acid  in  the  eclampsias 
is  greater  than  in  chronic  nephritis  or  the  nephritic  toxemias. 


SUMMARY 

Low  values  for  nonprotein  and  urea  nitrogen  are  found  in 
normal  pregnancy.  The  urea  nitrogen  constitutes  about  44  per 
cent  of  the  nonprotein  nitrogen.  No  variation  is  found  in  the 
uric  acid,  creatinin,  chlorid  or  sugar  concentration  of  the  blood  of 
normal  pregnant  women  from  that  observed  in  nonpregnant 
women.  A  slight  decrease  in  the  carbon  dioxid  combining  power 
of  the  blood  plasma  characterizes  the  last  months  of  normal  preg- 
nancy. 

The  chemical  changes  in  the  blood  in  the  nephritic  toxemias 
are  typical  of  impairment  of  kidney  function  in  general.  There 
is  an  increase  in  the  nonprotein  and  urea  nitrogen,  and  more  than 
50  per  cent  of  the  nonprotein  nitrogen  is  in  the  form  of  urea. 
There  is  a  decrease  in  the  alkali  reserve  of  the  blood,  but  no  greater 
than  that  observed  in  normal  pregnancy; 

Analogous  chemical  changes  are  found  in  the  blood  in  hyper- 
emesis, post-partum  eclampsia  and  eclampsia  with  gravid  uterus. 
The  nonprotein  nitrogen  is  markedly  increased  whereas  the  urea 
nitrogen  is  at  the  low  normal  limit  or  decreased,  constituting  but 
15  to  38  per  cent  of  the  nonprotein  nitrogen.  A  definite  increase 
in  uric  acid  is  found  which  is  due  to  an  impairment  of  renal  func- 
tion. In  some  cases  the  disturbance  of  kidney  function  resulted  in 
a  retention  of  urea  nitrogen  in  addition  to  the  uric  acid.  In  these 
types  of  toxemia,  the  involvement  of  renal  function  results  from 
the  toxemia.  A  moderate  or  severe  acidosis  is  observed  in  all 
cases.  A  prompt  improvement  judged  from  a  clinical  standpoint 
is  accompanied  by  a  return  to  a  normal  composition  of  the  blood. 
The  extent  of  the  toxemia  closely  parallels  the  increase  in  the 


i97 

rest-nitrogen,  as  judged  by  the  relation  of  the  urea  to  the  non- 
protein  nitrogen. 

/ 

LITERATURE 

ALLEN.    Journ.  A.  M.  A.,  1920,  74,  652. 

ALLEN,  STILLMAN  AND  FITZ.  Monographs  of  the  Rockefeller  Insti- 
tute for  Medical  Research,  No.  n,  New  York,  1919. 

BAUMANN,  HANSMAN,  DAVIS  AND  STEVENS.  Arch.  Int.  Med.,  1919, 
24,  70. 

CALDWELL  AND  LYLE.    Am.  Journ.  Obst,  1921,  2,  17. 

EMGE.    Am.  Journ.  Obst,  1918,  77.     Ibid.,  1916,  74. 

EWING.    Am.  Journ.  Obst.  and  Dis.  Worn.,  1905,  51,  145. 

EWING  AND  WOLF.    Am.  Journ.  Obst.,  1907,  55,  289. 

FOLIN.     Am.  Journ.  Physiol.,  1905,  13,  84. 

HASSELBACH  AND  GAMMELTOFT.    Biochem.  Ztschr.,  1915,  68,  207. 

JOSLIN.    The  Treatment  of  Diabetes.     Philadelphia,  1920. 

KAST  AND  WARDELL.    Arch.  Int.  Med.,  1918,  22,  581. 

KILLIAN.     Proc.  Soc.  Exper.  Biol.  and  Med.,  1917,  15,  17. 

KILLIAN  AND  SiiERWiN.    Am.  Journ.  Obst,  1921,  2,  6. 

LOSEE  AND  VAN  SLYKE.    Am.  Journ.  Med.  Sc.,  1917,  53,  94. 

MARRIOTT.    Journ.  A.  M.  A.,  1916,  66,  1594. 

MARRIOTT  AND  ROWLAND.    Arch.  Int.  Med.,  1916,  18,  708. 

MORRIS.     Bull.  Johns  Hopkins  Hosp.,  1917,  28,  140. 

MOSENTHAL  AND  HlLLER.      Journ.  Urol.,   1917,   I,  75- 

MYERS.    Practical  Chemical  Analysis  of  Blood.     St.  Louis,  1920. 
MYERS  AND  FINE.    Chemical  Composition  of  the  Blood  in  Health  and 

Disease.     New  York,  1915. 
MYERS  AND  FINE.    Journ.  Biol.  Chem.,  1919,  37,  239.    Ibid.  1915,  21, 

377.    Ibid.  1913,  16,  169.    Ibid.,  1913,  14,  39. 
MYERS  AND  KILLIAN.    Amer.  Journ.  Med.  Sc.,  1919,  97,  674. 
MYERS  AND  KILLIAN.    Journ.  Biol.  Chem.,  1917,  29,  179. 
MYERS  AND  SHORT.    Journ.  Biol.  Chem.,  1920,  44,  47. 
PALMER  AND  VAN  SLYKE.    Journ.  Biol.  Chem.,  1917,  32,  499. 
PLASS.     Bull.  Johns  Hopkins  Hosp.,  1917,  28,  137. 
SELLARDS.    The  Principles  of  Acidosis  and  Chemical  Methods  for  Its 

Study.    Cambridge,  Mass.,  1917. 

SLEMONS  AND  BOGERT.    Journ.  Biol.  Chem.,  1917,  32,  63. 
SLEMONS  AND  MORRIS.     Bull.  Johns  Hopkins  Hosp.,  1916,  27,  343. 


i98  TOXEMIAS  OF  PREGNANCY 

TILESTON  AND  COMFORT.    Arch.  Int.  Med.,  1914,  14,  620. 

UNDERIIILL  AND  RAND.    Arch.  Int.  Med.,  1910,  5,  61. 

VAN  SLYKE.    Joutn.  Biol.  Chem.,  1917,  30,  347. 

VAN  SLYKE  AND  STADIE.    Arch.  Int.  Med.,  1920,  25,  693. 

WHITE.    Lancet,  London,  1920,  2,  1248. 

ZWEIFEL.     Miinchen.  mecl.  Wchnschr.,  1906,  53,  297. 


ILLUSTRATIVE  CASE  REPORTS 

The  brief  descriptions  which  follow  are  taken  from  personal 
case  records  and,  while  very  much  condensed,  will,  it  is  hoped, 
demonstrate  typical  instances  of  some  of  the  many  variations  of 
the  toxemias  of  pregnancy. 

The  patients  were  seen  in  the  service  of  the  New  York 
Lying-in  Hospital  or  in  the  author's  private  practice,  unless  other- 
wise noted. 

Dates,  hospital  numbers  and  other  designations  are  purposely 
omitted  as  unnecessary. 

i.  Severe  Hyperemesis  in  First  Pregnancy  with  Complete  Absence 
of  this  Complication  in  Subsequent  Pregnancies. — The  patient,  in 
good  general  health,  a  para-i,  began  to  vomit  soon  after  skipping  a 
period  and  notwithstanding  treatment  her  condition  grew  rapidly 
worse.  From  being  a  well-nourished  girl  with  florid  complexion, 
she  lost  weight  rapidly  and  developed  a  marked  pallor  of  the  skin  which 
later  became  yellow  and  the  conjunctiva?  were  markedly  injected. 
The  patient  was  very  anxious  to  carry  out  her  pregnancy,  but 
when  she  began  to  vomit  large  quantities  of  coffee-ground 
material,  it  was  decided  to  empty  the  uterus.  This  was  done  in 
two  sessions  without  shock  and  the  patient  made  a  fairly  rapid 
recovery.  Subsequently  she  went  through  two  full-term  pregnan- 
cies without  any  vomiting  at  all.  In  each  case  the  labor  was 
rather  difficult.  In  her  fourth  pregnancy  she  began  to  vomit 
within  a  short  time  after  trie  missed  period.  Her  general  condi- 
tion was  fairly  good,  but  she  was  very  nervous  and  depressed. 
She  began  to  bleed  and  finally  passed  several  large  clots.  A  diag- 
nosis of  incomplete  abortion  was  made,  and  an  exploratory 
curettage  was  done.  A  moderate  amount  of  detritus  was  secured 
but  no  placenta  was  found.  Evidently  the  abortion  had  been 
fairly  complete.  Unfortunately,  the  softened  cervix  was  torn 
during  the  process  of  dilatation  and  the  patient's  subsequent 
recovery  was  marked  by  moderate  elevations  of  temperature 

199 


200  TOXEMIAS  OF  PREGNANCY 

with  the  production  of  a  pelvic  exudate.  The  final  recovery  was 
fairly  good,  however.  Why  this  severe  hyperemesis  should  have 
been  present  only  in  the  first  and  not  in  subsequent  pregnancies, 
could  not  be  determined.  There  were  evident  local  causes.  It 
is  interesting  to  note  that  with  the  reappearance  of  the  trouble 
in  the  fourth  gestation,  spontaneous  abortion  resulted. 

2.  Induction  of  Labor  for  Death  of  Fetus  and  Toxemia. — Patient 
age  twenty-four,  married  two  years,  had  a  spontaneous  miscar- 
riage at  the  end  of  her  first  year  at  two  months,  following  what 
was  diagnosed  at  the  time  as  a  "renal  infection."  In  her  second 
pregnancy  there  were  traces  of  albumin  from  the  beginning, 
although  her  general  health  was  apparently  good.  When  I  saw 
her  at  the  sixth  month  the  urine  showed  about  2  per  cent  albumin, 
but  no  casts.  The  blood-pressure  was  160  over  1 10.  An  effort  was 
made  to  carry  the  patient  along,  as  she  was  very  anxious  for  a 
child.  She  was  kept  in  bed  on  a  restricted  diet  and  after  an 
apparent  improvement  she  was  allowed  to  go  home.  Two  weeks 
later  the  baby  could  no  longer  be  felt  and  during  the  succeeding 
two  weeks  no  further  enlargement  of  the  uterus  seemed  to  take 
place.  As  the  patient  was  very  thin,  with  relaxed  abdomen,  this 
could  be  readily  noted.  Careful  examination  showed  no  evi- 
dences of  fetal  movements  or  heart  signs.  The  patient's  general 
condition  was  not  good.  She  complained  of  headaches,  nausea 
and  vomiting.  The  face  was  puffy  and  there  was  slight  edema  of 
the  hands  and  feet.  The  albuminuria  increased  and,  in  the  belief 
that  the  toxic  symptoms  were  due  to  a  combination  of  the 
nephritis  and  a  dead  fetus,  labor  was  induced  with  bags  and  after 
sufficient  dilatation  a  breech  extraction  of  a  macerated  six 
months'  fetus  was  performed.  The  placenta  was  found  to  be 
thickly  studded  with  infarcts,  one  of  which  measured  about  two 
inches  in  diameter.  It  is  likely  that  in  this  case  the  fetal  death 
could  be  ascribed  to  the  placental  degeneration  induced  by  the 
nephritis  in  the  mother.  A  year  later  the  patient  again  became 
pregnant.  During  the  interval  she  had  been  in  fairly  good  gen- 
eral condition,  having  gained  in  weight  since  her  previous  preg- 
nancy, but  as  soon  as  she  became  pregnant  again  her  condition 
immediately  grew  worse.  Nausea  and  vomiting  were  extreme. 
Headaches  and  visual  disturbances  were  constantly  present  and 
her  weight  diminished.  The  examination  of  the  urine  at  this  time 
showed  increasing  amounts  of  albumin  and  numerous  casts,  a 


ILLUSTRATIVE   CASE  REPORTS  201 

progressive  condition  which  it  was  not  thought  the  patient  could 
satisfactorily  overcome.  The  uterus  was  accordingly  emptied  and 
the  patient  made  a  fairly  prompt  recovery.  She  was  warned  not 
to  become  pregnant  for  several  years  and  to  place  herself  under 
competent  observation  at  the  very  beginning  of  her  pregnancy. 

The  patient  remained  in  good  general  health,  gained  weight 
and  became  pregnant  again  about  two  years  later.  Aside  from 
mild  nausea  and  vomiting  she  remained  apparently  well  until  the 
sixth  month  of  her  pregnancy,  when  the  urine,  which  had  con- 
tained only  slight  traces  of  albumin,  suddenly  contained  from  two 
to  four  grams  per  liter  and  numerous  hyalin  and  epithelial  casts 
appeared.  Under  the  care  of  her  family  physician,  her  condition 
improved  but  about  three  weeks  later  she  noticed  a  numbness  in 
the  right  arm  which  gradually  extended  upward  and  developed 
into  a  more  or  less  complete  paralysis  of  the  entire  limb  and  the 
pectoral  group  of  muscles.  Loss  of  speech  followed,  with  a 
paralysis  involving  the  tongue  and  right  side  of  the  face.  There 
was  no  period  of  unconsciousness.  The  patient  responded  to  ques- 
tions by  attempting  to  nod  her  head.  Both  pupils  reacted  equally 
to  light,  the  tongue  could  be  fully  protruded  but  the  tip  deviated 
to  the  left.  There  was  no  loss  of  tactile  sense  except  in  the  right 
arm  from  the  ringer  tips  to  the  shoulder.  The  limb  was  warm  to 
the  touch.  Swallowing  was  somewhat  interfered  with  although 
the  patient  was  able  to  take  liquids  slowly.  The  uterus  was  ap- 
parently that  of  6l/2  to  7  months'  gestation  and  the  fetal  sounds 
were  faintly  heard  over  the  lower  uterine  segment.  Fetal  move- 
ments were  distinctly  felt  by  patient.  Blood  pressure  160  systolic, 
90  diastolic.  The  condition  impressed  one  as  due  to  localized 
cerebral  edema  rather  than  actual  hemorrhage.  Patient  trans- 
ferred to  the  hospital  and  on  admission  the  urine  showed  10  grams 
per  liter  with  numerous  hyalin  and  granular  casts;  there  was  no 
acetone  or  diacetic  acid  present. 

Treatment  by  hot  packs  and  colonic  irrigations  with  glucose 
solution,  together  with  forced  carbohydrate  feeding  and  sedatives 
by  rectum  was  succeeded  by  a  gradual  improvement  in  the 
patient's  condition  until  all  evidences  of  paralysis  disappeared  one 
month  after  admission  to  the  hospital. 

The  abdominal  enlargement  did  not  seem  to  progress  and, 
although  the  patient  believed  she  was  over  seven  months'  preg- 
nant, the  fundus  corresponded  in  size  to  less  than  this  period, 


202  TOXEMIAS  OF   PREGNANCY 

Fetal  movements  were  distinctly  felt  and  heart  sounds  heard 
during-  this  time  and  then  ceased  suddenly.  After  several  days  of 
observation  it  was  thought  advisable  to  induce  labor  and  this  was 
completed  without  difficulty,  a  poorly  nourished  infant  of  about 
seven  months'  gestation  being  born.  No  abnormalities  were  pres- 
ent except  that  the  cord  was  around  the  neck  in  a  loose  coil  not 
sufficiently  tight  to  have  produced  constriction.  There  was  a 
slight  degree  of  maceration  of  the  epithelium  around  the  feet. 
The  placenta  was  easily  expressed  and  there  was  no  retroplacental 
clot;  post-partum  hemorrhage  was  slight.  The  placental  sub- 
stance was  thin  and  contained  numerous  infarcts,  making  up 
about  one-half  of  its  mass,  quite  typical  of  this  condition. 

The  patient  made  an  uninterrupted  recovery  and  was  dis- 
charged from  the  hospital  two  weeks  later  with  a  normal  urinary 
picture.  In  this  instance  it  is  very  unlikely  that  the  patient  will 
ever  carry  out  a  full-time  gestation. 

3.  Induction  of  Labor  for  Mild  Toxemia. — Patient,  a  para-i,  age 
thirty-five,  in  fairly  good  general  health,  presented  nothing  ab- 
normal until  the  seventh  month,  when  she  developed  some 
dyspnea,  had  repeated  slight  fainting  spells  and  became  very  nervous. 
The  blood-pressure  up  to  the  eighth  month  had  been  practically 
normal,  but  gradually  increased  until  the  systolic  pressure  was 
172  at  the  calculated  termination  of  her  pregnancy.  There  were 
no  evidences  of  labor  present  and  no  response  to  several  doses  of 
castor  oil.  Considerable  malaise  and  a  decided  yellow  tinge  to  the 
skin  and  sclera  became  prominent  symptoms  and,  although  the 
urine  examinations  were  negative,  the  picture  was  one  of  a  grad- 
ually increasing  toxemia.  Labor  was  induced  with  bags  and  pro- 
ceeded slowly,  a  forceps  extraction  being  done  when  the  head 
reached  the  perineum.  The  baby  was  large  and  vigorous.  The 
patient  made  a  slow  recovery,  although  the  involution  of  the 
uterus  proceeded  normally.  Several  months  later  a  diagnosis  of 
hypothyfoidism  was  made  and  considerable  improvement  resulted 
from  specific  treatment  for  this  condition. 

The  case  is  one  of  a  considerable  group  met  with  in  which  the 
endocrine  disturbances  centered  in  thyroid  anomalies  seem  to  be 
prominent.  Their  treatment  during  pregnancy  is  very  unsatis- 
factory and  little  improvement  occurs  until  after  delivery. 
Strange  to  say,  in  many  of  these  patients  the  babies  are  large  and 
well-nourished,  which  adds  considerably  to  the  difficulty  of  the 


ILLUSTRATIVE   CASE   REPORTS  203 

labor.  The  patients  present  evidences  of  toxemia  which,  although 
mild  in  degree,  are  continuous  and  always  require  careful  observa- 
tion of  the  patient,  with  a  resort  to  more  vigorous  treatment  when 
indicated,  including  the  induction  of  labor  if  the  patient  does  not 
spontaneously  go  into  labor  at  term. 

4.  Induction   of  Labor  for  Nephritic   Type   of   Toxemia. — The 
patient,  a  young  primipara  at  the  seventh  month,  had  been  under 
continuous  treatment  for  the  previous  two  months.     The  blood- 
pressure  at  the  beginning  was  about   180  and  accompanied  by 
puffiness  of  the  face  and  a  persistent  albuminuria  (from  4  to  6 
per  cent).    A  few  granular  casts  were  noted  occasionally.     There 
were  slight  visual  disturbances  and  considerable  headache.     At 
the  eighth  month  the  patient's  condition  did  not  improve  and  in- 
duction  of   labor   was   decided   on.      This   was   successfully    started 
with  bags,  but  the  patient  made  slow  progress  and  was  finally 
delivered  by  low  forceps.     The  baby  was  considerably  asphyx- 
iated,  but  was  finally  resuscitated  and,  although  weighing  less 
than  five  pounds,  did  very  well  on  artificial  feeding. 

The  patient  made  a  slow  recovery,  and  the  albumin  persisted 
for  some  months  after  delivery,  although  the  edema  disappeared 
more  promptly.  Labor  was  induced  in  this  instance  a  month 
before  term  because  it  was  felt  that  the  progressive  character  of 
the  nephritis  might  produce  irremedial  damage  if  the  patient  were 
allowed  to  go  for  an  indefinite  period. 

5.  Eclampsia  During  Midprcgnancy  in  a  Patient  with  Chronic 
Nephritis;   Exacerbation   in  Second  Pregnancy  with  Induction   of 
Labor  and  Delivery  of  a  Viable  Child. — The  patient,  a  primipara,  was 
seen  in  consultation  when  about  six  months'  pregnant,  with  a  his- 
tory of  having  had  three  general  convulsions,  after  the  first  of 
which    she    had   been    transferred    to    a   hospital.      Examination 
showed  a  stout,  well-nourished  girl  in  deep  coma,  with  marked 
puffmess  of  hands,  face  and  feet.     The  abdominal  fat  was  thick 
and  the  fundus  slightly  above  the  level  of  the  umbilicus.     There 
were  no  evidences  of  labor.     Previous  urinalyses  showed  increas- 
ing traces  of  albumin,  but  no  definite  treatment  had  been  Insti- 
tuted.    The  patient's  general  condition  seemed  unfavorable  for 
any  attempts  at  palliative  treatment,  so  induction  of  labor  was 
carried  out  by  means  of  Voorhees  bags  without  difficulty.    The  convul- 
sions continued  during  the  labor,  and,  after  sufficient  dilatation 
was  secured,  the  membranes  were  ruptured  and  the  *etus  ex- 


204  TOXEMIAS  OF  PREGNANCY 

tracted  with  the  hand.  It  weighed  about  one  pound,  was  about 
nine  inches  long  and  made  no  efforts  at  respiration.  The  patient 
made  a  very  slow  recovery  and  the  albumin  and  casts  persisted 
in  the  urine  for  many  weeks.  She  became  pregnant  again  about 
four  years  later  and  was  seen  in  consultation  at  the  sixth  month. 
Her  physician  had  carefully  watched  the  case  and  at  this  time, 
although  there  was  some  general  edema,  the  blood-pressure  was 
fairly  low  and  the  urine  did  not  contain  any  casts,  although  a 
moderate  amount  of  albumin  was  present.  In  view  of  the  desire 
for  a  living  child  an  attempt  was  made  to  carry  the  patient  along. 
Hospital  sojourn  was  instituted  and  the  patient  kept  in  bed  on  a 
carefully  regulated  low  protein  diet.  The  edema  and  slight  head- 
aches persisted,  but  the  blood-pressure  did  not  go  over  150  and 
only  slight  traces  of  albumin  with  few  casts  were  noted  in  the 
urine.  About  the  eighth  month  the  patient  complained  of  dizzi- 
ness and  one  evening  noticed  slight  twitching  movements  of  the 
hands  and  face.  The  general  condition  was  not  as  favorable  as 
during  the  previous  weeks,  and  labor  was  accordingly  induced 
with  Voorhees  bags.  Within  twenty-four  hours  the  patient  de- 
livered herself  of  a  small  but  vigorous  baby,  which,  after  a  pre- 
liminary bottle  period,  was  successfully  nursed.  The  patient 
made  a  very  satisfactory  recovery  from  this  labor  and,  although 
subsequent  urinalyses  showed  that  her  nephritis  was  not  recov- 
ered from,  her  general  condition  seemed  very  satisfactory.  The 
case  demonstrated  the  possibility  of  carrying  these  patients 
through  a  subsequent  pregnancy  notwithstanding  an  unfortunate 
previous  attempt. 

6.  Induction  of  Labor  for  Toxemia  and  Thyroid  Disturbances. — 
Patient,  a  para-i  of  neurotic  temperament,  went  through  a  very 
uncomfortable  pregnancy  marked  by  headaches  beginning  during 
the  early  months,  to  which,  after  the  sixth  month,  were  added 
visual  disturbances  and  swelling  of  the  hands  and  feet.  There 
were  marked  traces  of  albumin  in  a  urine  of  high  specific  gravity. 
When  the  patient  was  about  eight  months'  pregnant  the  condition 
of  hydramnios  and  edema  of  the  lower  part  of  the  abdomen  made 
her  very  uncomfortable.  The  patient  had  an  exophthalmic 
goiter;  by  advice  of  another  physician  thyroid  extract  was  ad- 
ministered continuously  at  this  time.  Her  general  condition,  with 
high  blood-pressure  and  unfavorable  urinary  signs,  called  for  inter- 
ference, and  labor  was  induced  with  Voorhees  bags.  The  response 


ILLUSTRATIVE   CASE  REPORTS  205 

was  unsatisfactory,  the  patient's  condition  becoming  rapidly 
worse.  Rupture  of  the  membranes  was  performed  when  the 
cervix  was  about  three  fingers  dilated  to  relieve  the  extreme 
abdominal  tension  and  also  in  the  hope  that  the  head  might 
engage.  No  progress  resulted  for  the  next  twenty-four  hours 
and,  as  the  patient  was  quite  exhausted,  no  engagement  of  the 
head  present,  the  cesarean  section  was  finally  decided  on  notwith- 
standing the  vaginal  manipulations.  It  was  a  last  resort  opera- 
tion and  performed  without  much  difficulty.  The  baby  was 
deeply  asphyxiated  at  the  time  of  extraction  and  resuscitation  was 
unsuccessful.  This  failure  could  be  attributed  to  the  intense 
uterine  contractions  produced  by  pituitrin  which,  contrary  to 
directions,  had  been  given  too  early  in  the  procedure.  Notwith- 
standing the  unsatisfactory  outlook,  the  patient  made  a  fairly 
good  and  rapid  recovery  from  her  operation.  The  evidences  of 
nephritis  persisted  for  several  months  and  the  condition  of 
asthenia  did  not  respond  well  to  tonic  treatment.  The  exophthalmus 
and  thyroid  enlargement  was  very  much  worse  six  months  after 
delivery  when  the  patient  disappeared  from  observation. 

7.  Induction  of  Labor  for  Hydramnios  with  Mild  Toxenna  and 
Thyroid  Disturbance. — Mrs.  P.,  at  or  near  term  in  her  second  preg- 
nancy, presented  an  extreme  degree  of  abdominal  distention 
which  had  been  progressing  for  the  previous  two  months. 
During  this  period  she  had  repeated  attacks  of  severe  headache 
and  dizziness,  combined  with  nausea  and  general  malaise,  to- 
gether with  a  moderate  swelling  of  the  hands  and  feet.  The 
right  lobe  of  the  thyroid  became  considerably  enlarged  during 
this  time  and,  although  the  termination  of  the  patient's  pregnancy 
was  not  calculated  until  a  month  later,  it  was  not  considered 
advisable  to  allow  her  to  continue  because  of  the  increasing  dis- 
tress. The  urine  at  this  time  showed  moderate  traces  of  albumin 
and  the  blood-pressure  was  moderately  high.  Labor  was  started 
with  a  No.  3  Voorhees  bag  and  completed  within  twenty-four 
hours.  Rupture  of  the  membranes  after  complete  dilatation  per- 
mitted the  escape  of  a  gallon  or  more  of  liquor  amnii  after  which 
the  labor  was  promptly  terminated.  The  baby  was  large  and 
well-nourished  and  the  placenta  normal.  The  symptoms  promptly 
disappeared  within  a  week  after  delivery,  but  the  thyroid  enlarge- 
ment progressed  and  about  a  year  later  a  partial  thyroidectomy 
was  performed  with  good  results.  During  this  patient's  first 


2o6  TOXEMIAS  OF   PREGNANCY 

pregnancy  a  much  less  degree  of  thyroid  enlargement  was  pres- 
ent, but  there  were  no  evidences  of  toxemia  like  those  that 
became  prominent  after  the  seventh  month  of  her  second  gesta- 
tion. 

8.  Doubtful  Eclampsia  with  a  Single  Convulsion. — Mrs.  -   — ,  a 
primipara,  was  admitted  to  the  hospital  with  a  history  of  having 
been  perfectly  well  until  she  went  into  labor  when,  during  the 
active  first  stage,  a  single  general  convulsive  seizure  occurred. 
The  patient  was  rushed  to  the  hospital  and  was  given  eliminatory 
and  sedative  treatment.     She  had  a  spontaneous  delivery  within 
a  few  hours.    There  were.no  further  convulsions  and  examination 
of  the  urine  showed  only  a  faint  trace  of  albumin  and  no  casts. 
There  was  no  elevation  of  blood-pressure.     It  is  doubtful  whether 
this  case  can  be  considered  a  true  eclampsia,  or  may  be  regarded 
purely  as  an  explosion  of  nervous  force  during  the  active  first 
stage  of  labor,  similar  to  what  we  see  in  young  children  who  often 
develop  a  convulsion  during  the  process  of  teething  or  otherwise. 

9.  Pre-edamptic  Toxemia  with  Induction  of  Labor,  Cervical  In- 
cision and  Forceps  Delivery. — The  patient,  a  para-i,  was  admitted  to 
the  hospital  during  the  seventh  month  of  her  pregnancy  with  a 
well-developed  nephritis.     She  was  kept  under  observation  for 
two  weeks,  but  very  little  improvement  followed  the  usual  dietary 
and    eliminant    measures.      Marked    puffiness    of    the    face    and 
hands  continued;  the  urine  contained  well-defined  traces  of  albu- 
min and  many  hyaline  and  granular  casts.     Examination  of  the 
eye-grounds  showed  considerable  edema  of  the  retina  but  no  hem- 
orrhages and  the  ophthalmologist  called  in  consultation  believed 
that  the  case  should  be  delivered.     The  induction  of  labor  was 
started  with  a  rectal  bougie  and  vaginal  pack.     The  cervix  was 
rigid,  scarcely  dilated,  but  on  removal  of  the  bougie  after  twenty- 
four  hours,  the  cervix  was  found  to  be  soft,  dilated  one  finger 
breadth  and  thinned  out.     A  No.  2  Voorhees  bag  was  next  intro- 
duced which  brought  on  regular  pains  and  was  expelled  about 
twenty-four  hours  later.     The  cervix  was  then  only  two  fingers 
dilated  and  rigid.    The  fetal  heart  became  more  rapid  and  during 
the  afternoon  the  rate  went  up  to  170.     The  patient  complained 
bitterly   of  headache  and  visual   disturbances.      In  view   of  the 
patient's  condition  and  also  that  of  the  child,  rapid  delivery  was 
decided  on,  and  under  light  anesthesia  the  anterior  lip  of  the  cer- 
vix was  incised  to  the  vaginal  vault.     A  sufficient  opening  was 


ILLUSTRATIVE  CASE  REPORTS  207 

secured  to  deliver  the  small  head  with  forceps.  The  baby  was 
markedly  asphyxiated  and  was  resuscitated  with  difficulty.  It 
was  small  and  poorly  nourished  and  died  subsequently  from  in- 
anition. The  placenta  was  the  site  of  many  infarcts  and  areas  of 
fatty  degeneration.  The  cervical  incision  was  immediately  closed 
and  was  satisfactorily  healed  at  the  time  of  discharge.  The  woman 
recovered  quickly  after  delivery  and,  in  view  of  the  small  and 
poorly-nourished  child,  more  time  could  have  been  allowed  for 
the  dilatation  of  the  cervix  rather  than  a  resort  to  a  cutting  opera- 
tion. The  latter  was  inspired  as  much  by  the  mother's  condition 
as  by  a  desire  to  save  the  child,  as  a  convulsive  seizure  seemed 
imminent.  The  eye  lesions  subsided  rapidly  after  delivery. 

10,  ii.  Confusion  of  Eclampsia  with  Encephalitis  Lethargica. — 
The  patient,  a  para-i,  was  admitted  to  hospital  with  a  history  of 
having  suddenly  developed  convulsions  at  the  seventh  month, 
which  were  followed  by  coma.  The  urinary  examination 
seemed  to  point  to  a  moderate  degree  of  toxemia  and  after 
twenty-four  hours  the  patient  recovered  from  her  coma.  The 
blood-pressure  was  not  high  and  a  temperature  of  about  102°  p., 
was  constant.  Within  twenty-four  hours  she  developed  further 
convulsions,  succeeded  by  coma  with  motor  and  sensory  dis- 
turbances of  the  extremities  and  rigidity  of  the  neck.  A  diagnosis 
of  either  cerebral  hemorrhage  or  meningitis  was  made  and  a  lum- 
bar puncture  was  performed.  The  fluid  showed  the  typical  char- 
acteristics of  the  encephalitis  epidemic  of  which  many  cases  had 
been  reported  at  that  time  in  New  York  City.  The  condition 
grew  rapidly  worse  with  deepening  coma,  increasing  temperature, 
delirium,  and  finally  death  within  about  three  days  after  admis- 
sion to  the  hospital.  The  diagnosis  of  encephalitis  was  confirmed 
by  the  consulting  neurologist  and  the  case  shows  the  necessity  of 
care  in  instituting  treatment  in  such  cases.  The  fetal  heart  was 
not  heard  at  any  time  and  the  patient  died  undelivered,  not  being 
considered  at  any  time  in  a  condition  for  operative  interference. 

In  another  case  admitted  to  the  hospital  at  the  same  time  with 
a  similar  history,  the  subsequent  course  was  very  much  milder 
and,  the  diagnosis  having  been  made,  the  patient  was  transferred 
to  Bellevue  Hospital.  She  was  at  about  the  seventh  month  of 
pregnancy  and  made  a  complete  recovery  and  was  readmitted  at 
term  to  the  Lying-in  Hospital,  where  she  delivered  herself  spon- 
taneously of  a  live  baby  and  made  an  uneventful  recovery.  In 


2o8  TOXEMIAS  OP  PREGNANCY 

this  case  also  the  general  impression,  even  before  the  neurological 
diagnosis  was  made,  was  that  the  case  was  not  a  toxemia  of  the 
type  ordinarily  met  with  in  pregnancy. 

12.  Cardiac  Disease  Associated  with   Toxemia  at   the  Seventh 
Month. — Mrs.  -    — ,  para-i,  was  admitted  to  the  hospital  with  a  his- 
tory of  dyspnea  on  exertion  which  came  on  rather  suddenly  two 
weeks  previously.     The  patient,  a  stout,  well-nourished  woman 
with  florid  complexion,  was  at  about  the  seventh  month  of  preg- 
nancy.    No  fetal  heart  was  heard  or  evidence  of  life  elicited.    The 
urine  contained  a  marked  trace  of  albumin  with  no  casts  except 
on  one  occasion.    The  blood-pressure  was  about  160.    The  patient 
was  markedly  dyspneic  on  admission  and  the  mucous  membranes 
cyanotic.      Examination   of   the    heart   showed    a   double    mitral 
murmur  with  marked  galloping  rhythm.     A  well-defined  area  on 
the  anterior  left  chest  presented  numerous  coarse  rales  and  what 
appeared  to  be  friction  sounds  over  the  cardiac  area  itself.     The 
apex  beat  was  moderately  displaced.     A  diagnosis  was  made  of 
endocarditis   complicating   the   pregnancy  with   partially   broken 
compensation  at  the  time  she  began  to  have  dyspnea  two  weeks 
previously.     The  high  blood-pressure  and  urinary  signs  pointed 
to  an   associated   toxemia,  but  the   serious   symptoms   could  be 
ascribed  to  the  former,  rather  than  to  the  latter,  lesion.     With 
rest  in  bed  the  signs  in  the  lungs  and  heart  rapidly  disappeared 
so  that  it  was  difficult  to  detect  any  murmur  three  days  later  when 
the  patient  went  into  labor  spontaneously  and  delivered  herself 
of   a   small,   poorly-nourished,    macerated   fetus   of   about   seven 
months'    gestation.      Examination   of   the   placenta   in    this   case 
showed  a  slight  degree  of  fatty  degeneration  but  no  other  visible 
abnormality.     The  patient  improved  rapidly  after  delivery,  and 
the  urinary  signs  disappeared  within   three  days,  although   the 
dyspnea  persisted.     This  case,  as  others,  shows  the  necessity  of 
making    a    careful    physical    examination    in    every    suspected 
eclamptic. 

13.  Pre-eclamptic  Toxemia,  with  Cesarean  Section. — The  patient 
was  admitted  to  hospital  for  observation,  complaining  of  head- 
aches and  marked  visual  disturbances.     She  was  a  para-i,  about 
thirty-five  years  of  age  and  apparently  about  seven  and  one-half 
months'   pregnant.      She   was   a   well-nourished   woman    inclined   to 
stoutness,  with  marked  edema  of  the  legs  and  puffiness  of  face  and 
hands.    Under  the  usual  eliminant  treatment  with  irrigations  and 


ILLUSTRATIVE   CASE   REPORTS  209 

hot  packs,  together  with  a  diet  restricted  largely  to  carbo- 
hydrates, a  rapid  diminution  in  the  urinary  albumin  occurred,  and 
also  in  the  number  of  casts.  The  patient  was  carried  along  for 
over  three  weeks  and  then  began  to  get  worse  again,  complaining 
of  severe  headaches  and  visual  disturbances,  including  transitory 
periods  of  actual  blindness.  The  urine  then  boiled  solid  and  in 
view  of  the  rapid  onset  of  the  symptoms,  cesarean  section  was 
decided  on,  as  the  cervix  was  elongated  and  undilated.  The 
cesarean  operation  was  performed  according  to  the  Davis  pro- 
cedure and  both  mother  and  baby  did  very  well.  On  the  tenth 
day  post  partum  the  patient  had  a  severe  coughing  spell  and  rup- 
tured the  uterine  wound  with  protrusion  of  the  intestines.  An 
immediate  closure  was  done  by  my  associate,  Dr.  L.  A.  Wing, 
who  stated  that  the  edges  of  the  wound  were  perfectly  clean. 
The  second  repair  resulted  in  a  firm,  satisfactory  closure.  During 
no  time  did  the  patient  have  any  temperature,  and  she  left  the 
hospital  in  good  condition  and  nursing  her  baby.  Failure  in  the 
union  in  the  abdominal  wound  has  been  noted  in  other  cases  of 
toxemia  delivered  by  cesarean  section,  where  no  evidences  of 
infection  can  be  found. 

14.  Fulminating  Eclampsia  with  Recovery  and  Subsequent  Death 
from  Cerebral  Hemorrhage. — A  primipara  at  about  the  seventh  month 
of  pregnancy  was  admitted  to  the  hospital  with  a  history  of  sud- 
den onset  of  general  convulsions.  There  was  no  record  of  pre- 
vious ante-partum  care.  The  patient  was  a  small,  well-nourished 
woman  in  coma,  with  moderate  swelling  of  hands,  feet  and  ankles. 
The  fundus  was  about  seven  months'  and  the  fetal  heart  sounds 
were  not  heard.  The  patient  had  several  convulsive  seizures  dur- 
ing the  next  two  days.  Repeated  doses  of  morphin  by  hypo- 
dermic seemed  to  exert  very  little  sedative  effect,  and  it  was  not 
until  the  rectal  administration  of  40  grains  of  chloral  and  60  grains 
of  sodium  bromid  that  the  patient  quieted  down.  She  was  so  rest- 
less that  it  was  impossible  to  administer  either  hot  packs  or  irriga- 
tions. After  quieting  down  as  the  result  of  the  rectal  administra- 
tion, packs  and  irrigations  were  given  twice  daily,  and  within 
twenty-four  hours  she  began  to  come  out  of  coma  and  in  a  few 
days  seemed  completely  recovered. 

The  urine  was  solid  on  admission  and  for  several  days  subse- 
quently and  then  quickly  cleared  up.  One  week  later  the  patient 
insisted  upon  going  home  and  became  very  much  excited  because 


2io  TOXEMIAS  OF  PREGNANCY 

of  the  noise  from  the  adjacent  delivery  room.  That  evening  she 
again  began  to  have  general  convulsions;  the  urine  boiled  solid 
and  no  response  to  treatment  was  obtained.  About  twenty-four 
hours  after  the  beginning  of  the  second  seizure  she  developed 
Cheyne-Stokes  respirations  and  died  in  coma  without  further  con- 
vulsions about  six  hours  later.  No  autopsy  was  permitted  in  this 
case.  The  picture  was  that  of  a  cerebral  hemorrhage,  probably 
into  one  of  the  ventricles  or  at  the  base  of  the  brain.  Spontaneous 
delivery  of  a  small,  living  baby  took  place  during  the  second 
attack,  the  patient  apparently  being  unaware  of  labor.  The  baby 
weighed  1,600  grams  and. lived  about  a  week. 

15.  Induction  of  Labor  for  Recurrent  Albuminuria. — The  patient 
was   feeling  well  but  was  admitted  to  hospital  for  observation 
because  a  routine  urine  examination  showed  solid  albumin  with 
many  hyaline  and  granular  casts.     No  general  symptoms  were 
present.    The  patient  was  given  a  light  carbohydrate  diet  and  the 
b 3\v els  were  thoroughly  cleared  out  with  castor  oil  and  enemas. 

.he  r.rinary  conditions  improved  and  for  several  days  there  was 
..  e.ely  a  trace  of  albumin,  but  a  sudden  recurrence  marked  by 
colid  albumin  and  a  complaint  of  malaise,  headache  and  dizziness 
prompted  the  induction  of  labor.  A  soft  rubber  rectal  tube  was 
inserted  through  the  rather  thick  cervix,  which  admitted  one 
finger,  and  within  twenty-four  hours  the  patient  delivered  herself 
spontaneously  of  a  vigorous  baby.  Within  a  few  days  the  urine 
cleared  and  the  patient  left  the  hospital  on  the  tenth  day  with  no 
albumin  or  casts. 

In  this  woman,  a  multipara,  evidently  near  term,  there  seemed 
to  be  no  reason  for  delaying  the  delivery  in  view  of  the  warning 
given  by  the  recurrence  of  the  albuminuria  and  the  development 
of  constitutional  symptoms. 

16.  Induction  of  Labor  for  Progressive  Toxemia. — The  patient, 
a  para-iv,  age  thirty-five,  with  a  history  of  profuse  menstruation 
and  a  toxemia  in  previous  pregnancies,  developed  a  moderate 
toxemia  about  the  sixth  month.     The  patient  was  stout,  appar-. 
ently  well  nourished,  and  with  regular  heart  action.     The  blood- 
pressure  was  164/108,  and  a  slight  systolic  murmur  was  present. 
After  a  week's  treatment,  including  colonic  irrigations,  diet  and 
rest  in  bed,  a  marked  improvement  resulted  and  the  patient  was 
dismissed  from  the  hospital.    At  the  end  of  June,  when  she  was  at 
about  the  eighth  month,  a  marked  swelling  of  the  legs  and  lower 


ILLUSTRATIVE   CASE   REPORTS  211 

• 

abdominal  wall  came  on,  with  headache  and  a  systolic  blood- 
pressure  of  180.  During  this  time  the  urine  contained  traces  of 
albumin  and  no  acidosis,  but  the  blood  showed  a  high  sugar  con- 
tent. In  view  of  the  general  discomfort  and  apprehension,  labor 
was  induced  with  bags  and  terminated  by  an  easy  low  forceps 
delivery.  The  baby  weighed  nine  pounds.  The  placenta  was 
very  thick,  showed  several  areas  of  fatty  degeneration  and  two 
cysts  of  about  an  inch  in  diameter  near  the  insertion  of  the  cord. 
The  outcome  might  have  been  less  favorable  in  this  case,  espe- 
cially for  the  child,  if  the  pregnancy  had  continued.  Stout  women 
of  this  type  developing  toxemia  are  not  good  risks. 

17.  Toxemia  at  the  Seventh  Month  with  Premature  Separation  of 
Placenta  at  Term. — A  private  patient,  age  thirty,  otherwise  well,  but 
stated  that  she  had  gained  over  twenty  pounds  since  her  marriage 
a  year  previously.  The  woman  was  very  stout  and  the  early  diag- 
nosis of  pregnancy  difficult.  An  adnexal  tumor  or  fibroid  was 
suspected  as  present  and  complicating  pregnancy.  The  patient 
went  along  under  careful  observation  until  September,  1921.  At 
this  time  she  began  to  complain  of  drowsiness  and  marked 
tingling  sensations  and  swelling  of  the  hands  which  kept  her 
awake  at  night.  Careful  urine  examinations  showed  a  low  specific 
gravity,  slight  traces  of  albumin  with  a  low  urea  output,  but  no 
casts.  A  moderate  degree  of  anemia  was  present  such  as  one 
might  expect  in  a  pale,  flabby  patient  of  this  type.  The  blood- 
pressure  at  no  time  was  over  140,  but  a  moderate  edema  of  the 
legs  developed.  Not  responding  to  the  usual  measures,  'the 
patient  was  sent  to  the  hospital  and  within  a  week  after  beginning 
radical  eliminant  treatment  with  colonic  irrigations  and  hot  packs, 
the  symptoms  rapidly  subsided  and  after  dismissal  the  patient 
complained  only  of  slight  tingling  sensations  in  the  hands.  A 
moderate  dyspnea  was  present  throughout  the  later  months.  The 
patient's  labor  was  calculated  for  October  30,  but  at  this  time 
there  were  no  evidences  of  its  appearance  and,  as  her  general  con- 
dition was  good,  it  was  decided  to  await  a  natural  termination  of 
the  pregnancy.  On  November  15,  1921,  the  patient  was  given 
two  ounces  of  castor  oil  with  good  result,  and  no  pains  were 
observed.  While  playing  cards  on  the  evening  of  the  following 
day  a  sudden  hemorrhage  occurred  without  pain.  Examination 
about  an  hour  later  showed  that  the  patient  had  bled  pretty 
freely.  The  vagina  was  full  of  clots ;  the  cervix  long,  rigid,  high, 


212  TOXEMIAS   OF   PREGNANCY 

slightly  dilated  but  no  presenting  part  was  felt.  The  pulse  was  good, 
though  somewhat  rapid.  The  patient  stated  that  she  had  not 
felt  any  life  since  six  o'clock  in  the  evening.  A  tentative  diag- 
nosis of  premature  separation  of  the  placenta  was  made,  with 
fetal  death.  The  patient  was  transferred  to  the  Women's  Hos- 
pital and  immediate  preparations  were  made  for  cesarean  section. 
Approach  was  made  through  the  median  high  incision,  and  no 
blood  was  found  in  the  free  peritoneal  cavity.  On  incising  the 
uterus  a  considerable  part,  of  the  placenta,  which  was  evidently 
free  from  the  uterine  wall,  protruded  into  the  wound  and  the 
placenta  itself  was  attached  along  the  right  side  of  the  uterus, 
extending  down  to  the  lower  segment.  On  rupturing  the  amniotic 
sac  it  was  found  filled  with  blood  and  the  child  when  extracted 
appeared  completely  exsanguinated.  The  uterus  contracted  well 
after  the  removal  of  the  placenta  and  was  the  site  of  at  least  a 
dozen  fibroid  nodules.  One  as  large  as  a  pigeon's  egg  in  the 
anterior  wall  appeared  to  be  breaking  down  and  it  was  therefore 
clamped  and  excised.  The  fetus  was  not  well  nourished  and  was 
completely  exsanguinated.  A  cause  for  the  latter  was  found  in 
the  velamentous  insertion  of  the  cord  into  the  upper  portion  of 
the  placenta  and  apparent  rupture,  allowing  the  fetal  hemorrhage 
to  take  place.  An  examination  of  the  placenta  showed  a  separa- 
tion of  several  finger  breadths  and  numerous  infarcts.  The 
patient  made  an  uninterrupted  recovery.  The  wound  healed  by 
primary  union,  there  was  no  shock,  and  the  urinary  conditions 
were  practically  .negative  throughout  the  puerperium. 

In  this  patient  we  were  evidently  dealing  with  a  moderate 
degree  of  toxemia  which  produced  alterations  in  the  placenta  that 
interfered  decidedly  with  the  nutrition  of  the  fetus.  The  vela- 
mentous insertion  of  the  cord  had  no  connection  with  the  toxemia 
and  it  is  doubtful  whether  enough  placental  separation  had 
occurred  to  kill  the  baby  had  it  not  been  for  the  rupture  of  the 
cord.  It  might  be  surmised  that  this  thinned-out  insertion  was 
torn  during  the  extraction,  but  the  distinct  statement  by  the 
patient  that  she  no  longer  felt  life  before  the  hemorrhage  took 
place  and  the  fact  that  no  heart  sounds  could  be  heard  pointed  to 
the  death  of  the  fetus  from  hemorrhage. 

18.  Marked  Toxemia  in  Middle  Months  of  Pregnancy. — The 
patient,  age  twenty,  para-i,  about  five  months'  pregnant,  was 
admitted  to  the  hospital  with  a  history  of  gradually  increasing 


ILLUSTRATIVE   CASE  REPORTS  '213 

edema  during  the  previous  weeks,  involving,  in  succession,  the 
lower  extremities,  hands,  face  and  labia.  The  latter  were  en- 
larged to  such  an  extent  that  micturition  was  difficult.  Examina- 
tion of  the  urine  showed  marked  traces  of  albumin,  a  moderately 
high  specific  gravity  and  many  hyaline  and  granular  casts.  The 
patient  was  under  observation  for  a  week  under  eliminant  treat- 
ment without  amelioration  of  symptoms.  Headaches  became 
more  marked  and  the  blood-pressure  averaged  160  systolic.  In 
view  of  the  youth  of  the  patient  and  the  early  appearance  of  the 
marked  nephritic  symptoms,  emptying  of  the  uterus  was  decided 
upon  as  giving  the  patient  a  better  chance  for  a  future  pregnancy 
before  serious  damage  to  kidneys  took  place.  Vaginal  hys- 
terotomy  was  followed  by  prompt  cessation  of  the  symptoms, 
lowered  blood-pressure  and  disappearance  of  the  edema. 

19.  Spontaneous    Abortion    during    Toxemia. — The    patient,    a 
para-iv,  age  thirty-four  years,  with  a  history  of  three  previous  normal 
labors  and  living  children.      In   the  fifth  month  of  her  present 
pregnancy  she  developed  severe  headaches,  epigastric  pain  and  a 
variety    of    nervous    symptoms.      The    patient    was    apparently 
neurotic,  although  she  appeared  well  nourished.     On  her  admis- 
sion to  the  hospital,  examination  disclosed  a  pregnancy  at  about 
the  fifth  month,  with  a  history  of  slight  bleeding.     The  blood- 
pressure,  which  was  180  on  admission,  diminished  with  rest  in  bed 
during  the  succeeding  week,  but  remained  about  150.   The  patient 
went  into  labor  spontaneously  and  delivered  herself  of  a  small, 
macerated  fetus.     The  urine  showed  marked  traces  of  albumin 
and  contained  many  hyaline  and  granular  casts.    The  termination 
of  pregnancy  in  toxemias  during  the  midmonths  is  not  unusual 
and,  as  in  this  case,  proves  a  satisfactory  conclusion  to  the  process. 

20.  Cesar  can  Section  for  Eclampsia  in  First  Pregnancy;  Second 
Pregnancy  and  Labor  Normal. — The  patient,  a  para-ii,  was  admitted 
to  the  hospital  at  eight  and  one-half  months  with  a  history  of  a 
previous  cesarean  section  for  the  termination  of  her  first  preg- 
nancy, with  living  child.    There  was  no  evidence  of  toxemia  dur- 
ing the  present  pregnancy.     The  patient  was  kept  in  bed  under 
careful  observation  and  went  into  labor  spontaneously,  apparently 
at  term.     The  membranes  were  ruptured  when  the  cervix  was 
two  fingers'  dilated  in  order  to  relieve  the  tension  on  the  uterine 
wall.     Dilatation  proceeded  rapidly,  the  head  came  down  to  the 
level  of  the  spines  and  the  delivery  of  a  normal  living  child  was 


2i4  TOXEMIAS  OF   PREGNANCY 

completed  by  forceps.  In  this  instance  the  cesarean  section  was 
done  by  another  operator  for  the  relief  of  severe  convulsions, 
evidently  with  a  satisfactory  outcome.  The  nonappearance  of 
evidences  of  toxemia  in  her  second  pregnancy  may  perhaps  be 
attributed  to  the  careful  ante-partum  observation.  The  case  also 
shows  the  advisability  of  keeping  these  patients  in  the  hospital 
under  observation  during  the  last  weeks  of  subsequent  preg- 
nancies and  the  fallacy  of  reliance  on  the  dictum:  "Once  a 
cesarean,  always  a  cesarean." 

21.  Convulsions   Due    to    Cerebral   Abscess   During   Pregnancy 
Which  Closely  Simulated  Eclampsia. — This  complication  was  well 
demonstrated  in  a  case  reported  by  Coughlin  in  the  Long  Island  Med- 
ical Journal,  March,  1921.     The  patient,  a  para-i,  age  twenty- four, 
suddenly  developed  general  convulsions  and  was  'admitted  to  the 
hospital  as  an  eclamptic  and  was  treated  accordingly.     A  macer- 
ated   fetus    was    spontaneously    expelled,    and,    after    labor,    the 
patient  went  into  a  condition  of  coma.    Within  a  few  days  menin- 
geal  symptoms  became  marked  and  the  patient  died.  The  autopsy 
showed  a  cerebral  abscess  and  the  infective  organism  was  a  diplo- 
coccus  intracellularis.     It  is  possible  that  in  this  case  a  condition 
of  sepsis  may  have  developed  after  delivery,  as  we  know  eclamptic 
patients  are  particularly  prone  to  sepsis,  but  in  all  probability  the 
cerebral  lesion  antedated  the  labor. 

22.  Faial  Case  of  Hepatic  Type  of  Eclampsia. — The  patient,  a 
para-i,  age  nineteen,  was  admitted  to  the  hospital  in  a  condition 
of  coma  which  followed  a  spontaneous  labor  with  forceps  delivery 
on   the   previous   day.      The   patient   had   apparently    been   well 
throughout  her  pregnancy  until  she  was  suddenly  seized  with 
convulsions,  of  which  there  were  a  total  of  twenty-one  before  she 
became  comatose.    A  diffused,  deep  jaundice  developed.    The  woman 
did  not  again  become  conscious  and  died  after  having  had  one  more 
convulsion  about  forty-eight  hours  after  delivery.    An  autopsy  showed 
a  large  liver  weighing  about  2,500  grams  and  presenting  numerous 
subcapsular  hemorrhages  scattered  over  its  entire  surface  (see  Fig.  16), 
and  in  addition,  there  were  many  hemorrhagic  areas  on  section  of  the 
organ.     A  microscopical  examination  showed  necrosis,  autolysis 
and  disintegration  of  the  hepatic  cells  of  the  central  two-thirds  of 
the  liver  lobule.    There  were  also  many  larger  hemorrhagic  areas 
throughout  the  liver  substance  which  destroyed  the  hepatic  cells 
from  pressure.    There  was  only  a  small  amount  of  fatty  degenera- 


ILLUSTRATIVE   CASE  REPORTS  215 

tion  present,  although  many  of  the  cells  showed  a  cloudy  swelling. 
The  kidneys  were  the  site  of  an  acute  diffuse  nephritis.  A  few 
petechial  hemorrhages  were  noted  in  the  spleen.  The  lungs  were 
edematous  and  many  of  the  air  cells  filled  with  blood.  This  was 
one  of  those  fulminating  cases  in  which  the  sudden  and  severe 
onset  precluded  a  satisfactory  prognosis  notwithstanding  the 
early  delivery  of  the  patient. 

23.  Induction  of  Abortion  for  Toxemia  in  the  Middle  Months  of 
Pregnancy. — The  patient,  a  para-iv,  age  twenty-two,  had  had  one 
stillborn  child  at  the  eighth  month  as  the  result  of  eclampsia  and 
another  five  months'  miscarriage.  The  woman,  although  stout 
and  apparently  well  nourished,  was  of  a  very  nervous  tempera- 
ment with  many  complaints,  including  insomnia,  restlessness, 
headaches,  etc.  Very  little  cooperation  was  secured  from  the 
patient  in  an  attempt  to  alleviate  her  condition.  The  headaches 
grew  steadily  worse  and  were  accompanied  by  visual  disturbances 
which  came  on  in  attacks  of  which  several  were  characterized  by 
periods  of  complete  blindness.  The  examination  of  the  eye- 
ground  was  not  satisfactory.  There  was  no  edema  at  any  time 
and  the  blood-pressure  remained  within  normal  limits.  The  pa- 
tient finally  went  into  labor  and  delivered  herself  spontaneously 
of  a  full-term  apparently  healthy  baby.  About  two  years  later 
she  again  became  pregnant  and,  when  she  reached  her  fourth 
month,  the  evidences  of  toxemia  again  became  marked.  The 
visual  disturbances  and  dizziness  were  accompanied  by  moderate 
traces  of  albumin  in  the  urine  and  many  hyaline  and  granular 
casts.  She  developed  a  considerable  edema  of  the  legs  and  hands 
and  her  general  nervous  condition  made  one  very  apprehensive 
as  to  the  final  outcome.  After  due  consultation  it  was  decided  to 
empty  the  uterus  and  this  was  done  after  two  cervical  packings 
with  gauze  and  a  small  Voorhees  bag.  After  sufficient  dilatation 
was  secured  the  membranes  were  ruptured  and  the  fetus  ex- 
tracted by  the  feet.  The  fetus  had  apparently  been  dead  for  some 
time,  as  the  head  came  away  during  the  process  of  extraction. 
A  spina  bifida  was  also  present  in  the  sacral  region. 

This  patient  had,  after  getting  up,  several  subjunctival  hemor- . 
rhages  and  since  then  has  occasionally  been   troubled  with  an 
exacerbation   of   the   nephritis,   including   attacks   of  headaches, 
dizziness,  swelling  of  the  feet,  etc.    This  woman  has  been  warned 
against  any  further  pregnancies. 


2i6  TOXEMIAS  OF  PREGNANCY 

24.  Eclamptic  Patient  Delivered  by  Vaginal  Cesarean  Section. — 
The  patient,  a  young  primipara  about  eight  months'  pregnant,  was 
well  during  the  entire  pregnancy  until  a  few  days  previous  to 
admission  to  the  hospital,  when  she  complained  of  headaches  and 
dizziness.     Several  convulsive  seizures  came  on  without, warning 
and  on  admission  the  patient  was  in  a  comatose  condition.    There 
were  no  signs  of  beginning  labor.    The  cervix  was  long,  rigid  and 
thick.  Additional  convulsions  occurred  and  there  was  no  response 
to  sedatives.     At  that  time  I  was  less  inclined  to  conservative 
measures  than  at  present  and  the  patient  was  prepared  for  deliv- 
ery by  a  vaginal  cesarean  section.    The  bladder  was  stripped  back 
after  making  an  incision  in  the  anterior  vaginal  fornix  and  then 
the  anterior  lip  of  the  cervix  was  cut  in  the  midline  down  to  the 
level   of  the   internal  os.     A   combined  version  was   performed 
without  difficulty  and  a  small,  feeble  child  extracted  which  died  a 
few  days  later.    The  uterus  contracted  firmly  and  there  was  little 
hemorrhage.     There  was  no  difficulty  in  this  instance  in  gaining 
sufficient  opening  in  the  lower  uterine  segment  to  do  a  version 
with  breech  extraction,  but  in  attempting  to  close  the  operative 
wound  considerable  difficulty  was  encountered,  as  the  upper  por- 
tion could  not  readily  be  approached  for  suturing;  in  fact,  this 
took  longer  than  the  delivery.     Although  I  had  done  a  series  of 
vaginal  cesarean   sections  on   similar  indications,   I  became  im- 
pressed with  my  experience  sufficiently  to  give  up  this  operation 
in  such  cases,  on  account  of  the  difficulties  of  suturing  and  the 
loss  of  time.     The  abdominal  cesarean  section  was  considered  in 
this  case,  but  on  account  of  the  number  of  vaginal  examinations 
previously  made,  it  was  not  thought  safe.     The  patient  finally 
made  a  satisfactory  recovery. 

25.  Induction  of  Labor  for  Chronic  Nephritis  with  Visual  Com- 
plications.— The    patient    was    about    eight    months    pregnant    when 
admitted  to  the  Misericordia  Hospital  with  a  history  of  increas- 
ing visual  disturbances  during  the  past  two  months.     Examina- 
tion by  a  prominent  ophthalmologist  disclosed  a  retinal  edema, 
with  impending  hemorrhages  and  induction  of  labor  was  advised. 

,  The  patient,  however,  was  carried  along  until  approximately  the 
eighth  month,  when  labor  was  induced  without  difficulty,  with  a 
Voorhees  bag.  Delivery  was  completed  with  a  low  forceps  ex- 
traction. A  small,  poorly-nourished"  ba"by  was  born,  which 
weighed  three  and  one-half  pounds  and  died  from  inanition  the 


ILLUSTRATIVE  CASE  REPORTS  217 

day  after  delivery.  The  placenta  did  not  show  any  gross  abnor- 
malities aside  from  its  thin,  flattened-out  character.  The  baby 
presented  the  typical  appearance  of  one  born  of  a  nephritic 
mother  and,  although  probably  somewhat  premature,  was  un*- 
doubtedly  unfavorably  affected  by  the  toxemia  of  the  mother. 
The  patient  made  a  slow  but  satisfactory  recovery.  The  albumin, 
casts  and  edema  persisted  for  some  months,  and  in  view  of  the 
patient's  history  and  the  severe  character  of  her  previous  preg- 
nancies, a  sterilization  by  the  abdominal  route  was  undertaken 
about  a  year  later  when  the  patient  presented  herself  again  at 
about  the  second  month  of  pregnancy.  The  uterus  was  first  emp- 
tied through  a  transverse  fundal  incision.  A  good  recovery 
resulted.  The  patient  in  this  last  pregnancy,  although  only  a 
few  months  advanced,  began  to  show  marked  traces  of  albumin 
in  the  urine,  together  with  many  casts,  and  serious  eye  symptoms 
also  appeared  as  in  the  previous  pregnancies.  In  view  of  these 
facts  it  was  not  thought  advisable  to  allow  her  to  continue  or  to 
be  subjected  again  to  impregnation. 

26.  Fated  Case  of  Eclampsia  of  the  Nephritic  Type. — A  para-ii, 
about  eight  months'  pregnant,  was  seized  with  severe  vomiting 
attacks  accompanied  by  headache.  On  the  same  day  several 
convulsions  came  on,  and,  on  admission  to  the  hospital,  the  patient 
was  in  moderate  coma.  The  pulse  was  weak  and  of  low  tension. 
The  fetal  heart  could  not  be  heard.  The  cervix  was  soft,  two 
fingers'  dilated,  and  the  head  in  the  brim.  Colonic  irrigations  resulted 
in  the  passage  of  a  large  amount  of  very  foul  fecal  matter.  The  urine 
specimen  boiled  solid.  Spontaneous  delivery  of  a  normal  stillborn,  full- 
term  fetus  followed.  •  A  few  slight  convulsions  were  noted  after 
delivery,  but  the  coma  was  continuous.  There  was  a  little  inv 
provement  on  the  next  day  and  the  patient  apparently  reacted 
well  to  the  treatment,  but  within  twenty-four  hours  after  delivery 
the  temperature  began  to  go  up  and  the  coma  returned.  Several 
severe  convulsions  occurred  throughout  the  night.  The  temper- 
ature rose  to  106°  F.,  the  pulse  tension  increased,  and  the  respira- 
tions became  shallow,  but  the  color  remained  good  and  there  was 
no  jaundice.  A  venesection,  followed  by  the  instillation  of  1,500 
cubic  centimeters  of  normal  salt  solution,  was  without  result.  The 
convulsions  continued  and  the  patient  died  the  next  day.  A  study 
of  this  case  seemed  to  point  to  an  overwhelming  toxemia  with  a 
probable  basilar  hemorrhage  or  general  cerebral  edema  coming 


2i8  TOXEMIAS  OF  PREGNANCY 

on  after  the  period  of  improvement  on  the  day  of  labor.  Inquiry 
disclosed  the  fact  that  the  patient  suffered  from  extreme  constipa- 
tion throughout  her  pregnancy,  and,  although  she  did  not  feel 
well  before  the  final  fatal  attack,  no  urine  examinations  were 
made  and  nothing  further  done  until  the  convulsions  developed. 

I  would  have  considered  salt  solution  contra-indicated  if  this 
case  had  come  under  my  care  during  recent  years,  since  I  have 
adopted  glucose  solutions  for  this  purpose. 

27.  Eclampsia  with  Induction  of  Labor,  Version,  and  Death  of 
Patient. — The  patient,  a  para-vi,  about  seven  months'  pregnant,  had 
been  showing  considerable  albumin  and  casts  in  the  urine  for 
which  treatment  had  been  given  with  apparently  little  result. 
She  complained  of  severe  headaches  and  indigestion  and  when 
seen  in  consultation  had  had  a  general  convulsion  followed  by 
coma.  Two  further  convulsions  occurred  before  the  patient  could 
be  sent  to  the  Woman's  Hospital.  The  systolic  blood-pressure 
was  152,  the  respirations  about  15  per  minute,  and  the  pulse  good 
and  full.  The  cervix  was  one  finger  dilated,  the  vertex  presenting, 
and  the  fetal  heart  heard.  Against  my  better  judgment  I  was 
prevailed  upon  to  proceed  with  the  induction  of  labor.  This  was 
carried  out  with  a  Voorhees  bag.  The  dilatation  was  fairly  prompt 
and  within  a  few  hours  the  cervix  was  thinned  out  and  four  fingers' 
dilated.  The  patient's  general  condition  during  this  time  became 
worse,  the  respirations  being  more  superficial  and  the  pulse  rapid. 
Although  there  were  no  further  convulsive  seizures,  irregular 
twitching  movements  of  the  hands  were  noted.  Moderately 
strong  uterine  contractions  were  present  and  after  the  cervix  was  thor- 
oughly dilated  the  membranes  were  ruptured,  a  version  done  and 
the  small  child  extracted  without  difficulty.  Considerable  bleed- 
ing followed  the  delivery  of  the  placenta  which  seemed  to  be  con- 
trolled, however,  by  the  injection  of  I  c.c.  of  pituitrin.  Soon 
after  the  patient  was  returned  to  bed,  bleeding  began  again  and 
several  clots  were  expelled.  A  careful  examination  was  made 
as  the  patient  was  not  yet  out  of  the  anesthesia,  but  no  cause  for 
the  hemorrhage  was  found  and  no  further  bleeding  occurred. 
The  patient,  however,  did  not  rally.  The  pulse  was  weak,  less 
than  100,  and  there  was  no  response  to  cardiac  stimulation. 
Within  an  hour  the  patient's  condition  suddenly  grew  worse  and 
the  picture  was  that  of  sudden  death  from  embolism.  No  autopsy 
was  permitted.  The  baby  weighed  three  and  one-half  pounds, 


ILLUSTRATIVE  CASE  REPORTS  219 

cried  feebly,  and  died  a  few  hours  later.     The  placenta  was  thick 
and  showed  marked  fatty  degeneration. 

In  this  case  the  shock  of  the  delivery  undoubtedly  contributed 
to  the  fatal  ending,  and  I  believe  a  better  outcome  would  have 
attended  the  use  of  palliative  measures. 

28.  Diabetic    Coma   Diagnosed    as   Eclampsia. — The    patient,    a 
para-i,  six  months'  pregnant,  was  admitted  to  the  hospital  in  a 
condition  of  coma  which  was  diagnosed  by  her  attending  physi- 
cian as  due  to  eclampsia.     The  patient  had  not  been  under  care- 
ful   observation,    and    the    previous    history    was    uncertain    but 
evidently  no  satisfactory  urinalyses  had  been  made.     The  woman 
was   a    small,    emaciated-looking   person   with    parched   lips    and 
tongue,  breathing  stertorously,  but  had  none  of  the  usual  ear- 
marks of  a  woman  who  had  had  either  a  convulsion  or  was  the 
subject  of  a  coma  usually  associated  with  eclampsia.     The  urine 
on  admission,  showed  about  4  per  cent  of  sugar,  with  a  trace  of 
albumin,  no  casts  and  a  high  specific  gravity,  together  with  well- 
marked  acetone  and  diacetic  acid  reactions.    Alkaline  therapy  was 
at  once  instituted.     The  patient  recovered  partially  a  few  hours 
later  and  manifested  an  intense  thirst.    After  a  preliminary  period 
of  starvation  she  was  given  fats  and  proteins  together  with  six 
drams  of  soda  bicarbonate  daily.     The  blood-sugar  after  fasting 
was  0.4  per  cent.     Slight  improvement  was- noted  during  the  next 
few  days  and  the  patient  became  quite  rational.    The  urinary  and 
blood-sugar  determinations  showed  a  decrease.     It  was  difficult 
to  examine  the  patient,  who  became  more  or  less  irrational  and 
then  went  into  labor,   delivering  herself  spontaneously  of  a  small, 
slightly  macerated  fetus  of  about  six  months'  gestation.     Soon 
after  labor  the  condition  of  coma  returned  and  no  response  to 
treatment  was  secured,  death  coming  on  within  forty-eight  hours 
after  delivery. 

This  case  is  probably  a  duplicate  of  many  others  in  which  a 
diagnosis  of  eclampsia  is  made  from  the  presence  of  coma  with 
occasional  convulsions  before'  a  urinalysis  shows  the  true  con- 
dition of  affairs.  The  sudden  loss  of  consciousness  in  diabetics 
is  not  unusual,  particularly  in  pregnancy,  where  the  disease  is  apt 
to  make  rapid  progress. 

29.  Numerous  Eclamptic  Convulsions  zvith  Recovery  after  Sed- 
ative Treatment. — The  patient,  a  primipara,  in  the  seventh  month  of 
her  pregnancy,  was  found  unconscious  on  the  floor  of  her  apart- 


220  TOXEMIAS  OF  PREGNANCY 

ment.  She  had  evidently  had  many  convulsions,  as  the  tongue 
was  greatly  lacerated  and  there  were  numerous  bruises  over 
the  body.  While  in  the  act  of  transferring  the  patient  to  the 
hospital  she  became  increasingly  restless  and  it  was  difficult 
to  restrain  her.  More  than  a  grain  of  morphin  was  given  by 
hypodermic  before  she  became  quiet.  Irrigations  and  packs  were  then 
instituted,  but  the  convulsive  seizures  during  the  next  twenty-four 
hours  totaled  seventeen.  A  gradual  improvement  took  place,  and 
a  week  later  the  urine  had  cleared  up  sufficiently  to  present 
merely  a  trace  of  albumin  with  a  few  casts.  The  puffiness  of  the 
face  and  hands  was  gone  and  the  patient  was  able  to  sit  up  in  bed. 
The  eliminant  treatment  was  kept  up,  however.  Fetal  movements 
and  heart  sounds  were  noted  for  a  week  after  admission,  when 
they  ceased,  and  at  the  close  of  the  second  week  labor  came  on 
spontaneously.  The  patient  was  in  the  midst  of  a  pack  when  she 
called  to  the  nurse  who,  on  lifting  the  blankets,  found  the  fetal 
head  had  already  been  expelled.  A  poorly-nourished,  macerated 
fetus  was  expelled,  followed  by  a  thick  placenta  with  numerous 
areas  of  fatty  degeneration  and  infarct  formation.  The  patient 
then  made  an  uninterrupted  recovery. 

The  point  of  interest  in  this  case  is  the  large  number  of  con- 
vulsions. As  I  stated,  seventeen  were  counted  after  admission 
and  the  appearance  of  the  patient  showed  that  she  had  evidently 
had  a  great  many  before  she  was  transferred  to  the  hospital.  The 
violence  of  the  attack  would  have  called  for  accouchement  force  or 
operative  delivery  under  ordinary  circumstances,  but  sedative  treat- 
ment certainly  was  more  satisfactory  in  the  end  than  the  shock  of  a 
forcible  or  operative  delivery  with  a  small,  under-nourished  child  that 
probably  would  not  have  survived. 


INDEX 


Abortion,    spontaneous   during  toxemia, 
213 

—  induction  of,  99 

—  before   operation   in   toxic  patient, 

acidosis  must  be  combatted,  103 

—  method,  100-102 

—  shock,  103 

—  should  not  be  delayed  beyond  cer- 

tain time,  100 

—  vaginal  hysterotomy  in  primiparae, 

1 02 

—  when  advisable,  99 

Acidosis,  in  relation  to  chemical  changes 
in  blood,  177 

—  in  urinary  conditions,  155 

—  urinary  analysis  of,  159 
Acute  yellow  atrophy  of  liver,  109 

—  charts,   120 

—  liver,  showing  swollen  turbid  cells, 

143 

—  section  of  kidney,  69 

—  section  of  liver,  67 

section  of  liver  under  high  power, 

68 

—  chemical  changes  in  the  blood  during, 

182,  183 

—  etiology  and  symptomatology,  20 

—  bacterial  theory,  21 

—  differential  diagnosis,  20 

—  jaundice,    as    an    accidental    symp- 

tom, 20 

—  must    be    distinguished    from    hy- 

peremesis,  20 

—  persistent     icterus     regarded    with 

apprehension,  20 

—  prognosis  of,  57 

—  pathology,  66 

—  hepatic  lesions,  66 

—  renal  lesions,  66 

—  Schwangerschaftsleber,     or     preg- 

nancy liver,  69 

—  treatment,   109 

—  little  can  be   said,  as  prognosis  is 

too  severe,  109 

—  uterus    should    be    emptied    imme- 

diately, 109 

Adrenalin  chlorid,  use  of,  in  hypereme- 
sis,   107 


Albumin  and  casts,  urinary  analysis  of, 

in  toxemias;  157 

Albuminuria,  associated  with  many  preg- 
nancies, 21 

—  charts  showing  placenta,  37,  39 

—  induction  of  labor  for  recurrent,  216 
Alkali  reserve,  in  blood,  175 

—  decrease  in,   found  in  eclampsia  and 

hyperemesis,  176 

—  large  quantities  of   acids  handled  in 

body  without  a  drop  in,  176 

Amberg,  practice  of,  in  the  eighteenth 
century,  2 

Amino-acids,  in  urinary  conditions  of 
toxemias,  155 

Ammonia  coefficient,  in  urinary  condi- 
tions in  toxemias,  154 

Anaphylactic  reaction,  in  relation  to 
eclampsia,  47 

Angioneurotic  edema,  57 

Auto-intoxication,  as  a  principal  etiolog- 
ical  factor,  14 


Bile  pigment,  found  in  urine  due  to 
hepatic  necrosis,  155 

-    urinary  analysis  of,   159 

Blood,  acidosis,  in  relation  to  alkali  re- 
serve, 177 

—  acute  yellow  atrophy  of  liver,  chem- 

ical changes  in,  182,  183 

—  alkali  reserve,  175 

decrease    in,    found    in    eclampsia 

..nd  hyperemesis,  176 
large  quantities  of  acids  handled  iri 

body  without  a  drop  in,  176 

—  carbon  dioxid,  how  determined,   177, 

178 

—  table  showing  combining  power  of, 

178 

—  changes  of,  in  normal  pregnancy,  178, 

179 

—  chemical  changes  in,  summary  of,  196, 

197 

—  chlorids,  173-175 

—  deficiency  of   excretion  of,   causa- 

tive factor  in  producing  edema, 
174 


222 


INDEX 


Blood,  chlorids,  determination  made 
upon  whole  blood  rather  than 
upon  plasma,  174 

—  creatiriin,  171 

—  eclampsia,  chemical  changes  in,   186- 

196 

—  hyperemesis,     chemical     changes     in, 

183-186 

—  nephritic    toxemia,    chemical   changes 

in,  179,  181 

—  nonprotein  nitrogen,  167 

—  distribution  of,  169 

—  retention  of,  167,  169 

—  rest-nitrogen,  169 

—  significant  chemical  changes,   166-198 

—  table    showing    comparative    nitrogen 

partition  of,  170 

—  urea  nitrogen,  169 

—  uric  acid,  170 

—  increase  of,  171 

—  retention  of,  171 

Blood-pressure,  associated  with  eclamp- 
sia disposes  to  hemorrhages,  80 

—  auscultatory   method   personally   pre- 

ferred, 31 

—  care  of,  in  eclampsia,  115 

—  individual    patient   should   always   be 

considered,  31 

—  in  relation  to  toxemias,  30 

—  significance  of,  30-32 

—  taking  ante-partum,  31 
Blood  transfusions,  108 

—  in  eclampsia,  133 

Calcium  salts,  abstraction  of,  46 
Carbohydrates,    effect   of   a  poison   les- 
sened if  taken  with  a  dose  of  glu- 
cose, 136 

—  in  treating  toxemias,   135 

Carbon    dioxid,    decrease    in   combining 
power  of,  in  eclampsia,  192 

—  how  determined  in  blood,  177,  178 
table  showing  combining  power  of, 

178 
Cardiac  disease  associated  with  toxemia, 

208 
Cases,    demonstrating    typical    instances 

in  toxemias,  199-220 
Cerebral    abscess,    case    of    convulsions 

due     to,     which     closely     simulated 

eclampsia,  214 
Cerebral  edema,  80 
Cerebrospinal  fluid,  195,  196 

—  study  of  the  nitrogen  distribution  of, 

in  eclampsia,  195 

—  urea  nitrogen  and  uric  acid  in,  195 
Cervical  canal,  stenosis  of,  92 


Cervical  erosions,  cauterization  of,  93 
Cesarean  section,  case  of,  in  pre-eclamp- 
tic  toxemia,  208 

—  for  eclampsia  in  first  pregnancy,  sec- 

ond  pregnancy    and    normal   labor, 
213 

—  when  justifiable,  128 

Charts,  ammonia  coefficient  in  two  suc- 
cessive pregnancies,  17 

—  blood  pressure,  from  a  pre-eclamptic, 

101 

—  showing  little  effect  from  vera- 
trum  viride,  120 

—  from  case  of  eclampsia,  100 
in  eclampsia  with  twins,  102 

—  brain,    laid    open,    in    eclampsia   with 

convulsions,  80 

—  comparison   of    the    nonprotein,   urea 

nitrogen  and  uric  acid,  etc.,  194 

—  cross  section   of   liver   showing  peri- 

portal  necrosis,  75 

—  incidence    of    eclampsia    in    different 

seasons,  25 

—  kidney  of  a  dog  after  seven  and  one- 

half    hours    chloroform    anethesia, 
138 

—  liver,  acute  yellow  atrophy,  143 
eclampsia,  showing  cloudy  swelling 

of  cells,  142 

eclampsia  showing  swollen  cells, 

141 

eclamptic  showing  diffuse  subcap- 

sular  hemorrhage,  73 

from  a  case  of  toxemia  after  in- 
travenous glucose  injection,  140 

of  a  dog  after  two  hours  of  chloro- 
form anesthesia,  139 

—  showing    extended    distribution    of 

subcapsular  hemorrhages,  74 

—  section    of    kidney,    from    a   case    of 

eclampsia    showing   parenchyma- 
tous  lesions,  71 

—  in  acute  yellow  atrophy,  69 

—  from  dog  subjected  to  chloroform 

anesthesia,  137 

showing  tubules  filled  with  Hyaline 

and  granular  detritus,  72 

—  section     of     liver,     in     acute    yellow 

atrophy,  67 

—  in  eclampsia,  77 

—  in  eclamptic  under  high  power,  76 

—  showing  central  necrosis,  64 
under  high  power  in  acute  yellow 

atrophy,  68 

—  section   of  placenta,   in    albuminurea, 

37- 
in  severe  albuminuria,  39 


INDEX 


223 


Charts,  sections  showing  two  stages  in 
infarction  process,  38 

—  table  of  cases  showing  glycemia  curve 

estimations,  144,  145 

—  table  of  significant  chemical  changes 

in  blood  in  disease,  168 

—  table    showing    chemical    changes    in 

blood  during  hyperemesis,  184 

—  table  showing  CO2  combining  power 

of  blood  plasma  in  normal  subjects 
and  in  acidosis,  178 

—  table    showing    comparative    nitrogen 

partition  of  blood,  170 

—  table  showing  retention  of  uric  acid, 

urea  and  creatinin  in  nephritis,  172 

—  urinary  conditions,  in  case  of  neurotic 

vomiting,  16 

—  in  toxemic  vomiting,  18 

—  showing    total    nitrogen    ammonia 

and  albumin,  32 

—  view    of    the    brain    in    post-partum 

eclampsia,  79 
Chemical  changes,  in  blood,  178 

—  acidosis,  177 

—  acute    yellow    atrophy    of    liver,    182, 

183 

—  alkali  reserve,  175 

—  decrease  in,  found  in  eclampsia  and 

hyperemesis,  176 

—  large  quantities  of  acids  handled  in 

body  without  a  drop  in,  176 

—  analysis  of,  166 

—  knowledge  of   diastatic  activity  of 

great  value,  166 

—  carbon  dioxid,  how  determined,   177, 

178 

—  table  showing  combining  power  of, 

178 

—  chlorids,  173-175 

deficiency  of   excretion   of,   causa- 
tive  factor  in  producing  edema, 

174 

—  determination    made    upon    whole 

blood  rather  than  upon  plasma, 

174 

—  creatinin,  171 

—  in  eclampsia,  186-196 

—  in  hyperemesis,   183-186 

—  in  nephritic  toxemia,  179,  181 

—  table  showing  chemical,  180 

—  in  normal  pregnancy,  178,  179 

—  nonprotein  nitrogen,  167 
distribution  of,  169 

—  retention  of,  167,  169 

—  rest-nitrogen,  169 

—  serve    as    a    guide    in    diagnosis    and 

treatment,  166 


Chemical  changes,  summary  of,  196,  197 

—  table  showing,.  168 

—  urea  nitrogen,  169 

—  uric  acid,  170 

—  increase  of,  171 

—  retention  of,  171 

Chlorids,  analysis  of,  in  urinary  condi- 
tions in  toxemias,  156 

—  in  blood,  173-175 

— • — -deficiency  of  excretion  of,  is  causa- 
tive  factor  in  producing  edema, 

174 

determination    made    upon    whole 

blood  rather  than  on  plasma,  174 

—  in  eclampsia,  191 

Chorea,     differentiation     of     eclampsia 
from,  53 

—  mortality  of,  in  pregnancy,  53 

—  symptoms  of,  in  pregnancy,  53 
Complex  protein,  as  introduced  into  the 

general     circulation     during     preg- 
nancy, 48 
Convulsions,  eclampsia  without,  29 

—  cerebral,  54 

—  hysterical,  54 

—  treatment  of,  116,  117 

—  word  superseded  by  "eclampsia,"  2 
Corpus  luteum  extract,  95 
Creatinin,  in  blood,  171 

—  in  eclampsia,  191 

—  product  of  "wear  and  tear"  of  tissues, 

173 

Delivery,  119 

Diabetic  coma,  diagnosed  as  eclampsia, 

219 
Diet,  influence  of  war,  on  eclampsia,  50 

—  schedule  of,  in  hyperemesis,  95 

—  variations  in,  51 

—  varied,   of    today,    deficient   in   phos- 

phorus and  calcium,  47 
Drugs,  sedative,  use  of,  107,  108 
Duhrssen,   mortality   rate    in   eclampsia, 

126 

Eclampsia,  as  prevalent  among  poor  as 
rich,  5 

—  case  closely  simulating,  214 

—  case   of,    during   midpregnancy,   with 

chronic  nephritis,  203 

—  cesarean    section    for,    second    preg- 

nancy and   labor   normal,    case   of, 

213 

—  charts,  blood-pressure,  with  twins,  102 

—  in     which    rapid     delivery    was 
done,  loo 


224 


INDEX 


Eclampsia,  charts,  brain  laid  open,  with 
convulsions,  80. 

—  case  of  acute  toxemia,  chart  show- 

ing, 40 

case  of,  showing  total  nitrogen 

ammonia  and  albumin  in  urine, 
32 

cross  section  of  liver  showing  peri- 
portal  necrosis,  75 

liver,  after  intravenous  glucose  in- 
jection, 140 

—  showing  cloudy  swelling  of  cells, 

142 

*- — • —  showing  extended  distribution  of 
subcapsular  hemorrhages,  74 

showing  extensive  diffuse  sub- 
capsular hemorrhage,  73 

—  showing  swollen  cells,  141 
placenta,  section  of,  from  case  of, 

38 
section    of   kidney,    showing   acute 

parenchymatous  lesions,  71 

—  ^—  showing  tubules  filled  with  Hy- 

aline,  72 
section  of  liver,  from  case  of,  77 

—  under  high  power,  76 

section  of  placenta  from  case  of 

albuminuria,  37 

severe  albuminuria,  section  of  pla- 
centa in  case  of,  39 

table,  showing  chemical  changes  in 

blood  in,  188,  189 

showing  glycemia  curve  estima- 
tions, 144,  145 

view  of  the  brain  in  post  partum, 

79 
—  chemical  changes  in  blood,  166 

—  chlorids,  181 
creatinin,   191 

decrease  in  combining  power  of 

carbon  dioxid,  192 

determination  of  uric  acid  as  index 

of  disturbance  of  kidney  func- 
tion, 190 

explanation  of  table  showing,  186 

—  high  nonprotein  nitrogen,  186 

—  hyperglycemia,  192 

in  hyperemesis  analogous  to  those 

in  post  partum,  193 
—  kidney  function  cause  of  increase 

in  urea  nitrogen,  190 
nonprotein     nitrogen     distribution, 

193 

—  table  showing,  188,  189 

—  umbilical  vein  and  artery,  194 

urea  and  rest  nitrogen,  187 

uric  acid  concentration,  187 


Eclampsia,  chemical  changes  in  blood, 
confusion  of,  with  encephalitis 
lethargica,  207 

• —  death  may  be  terminal  manifestation 
of  a  series  of  symptoms,  13 

—  derivation  of  the  word,  i 

—  diabetic  coma  diagnosed  as,  219 

—  doubtful,  with  a  single  convulsion,  206 

—  earlier  description  of  a  disorder  now 

recognized  as,  8 

—  etiology  and  symptomatology,  13 
abortions  and  premature  deliveries 

resulting  from  diseased  endome- 

trum,  50 
administration  of  sedatives  reduces 

number  and  severity,  28 
—  as  an  anaphylactic  reaction,  47 
associated  with  abnormal  forms  of 

gestation,  24 

—  best  results  attend  cases  coming  on 

during  labor,  27 
blood-pressure,  30 

—  blood-pressure  over  130°  should  be 

closely  observed,  30 

—  —  calcium  salts,  abstraction  of,  as  a 

cause  of  toxemia,  46 

—  case  of,  reported  by  E.  P.  Watson, 

24 

caused   by   abstraction   of    calcium 

salts  from  mother  by  fetus,  46 

—  cessation  of  symptoms  with  death 

of  the  child,  36 
chorea,  differentiation  from,  53 

—  —  clinical  course,  27 

considerations  as  to  early  autolysis 

of  placenta,  36 

course  of  a  seizure  of,  28 

criticism    of    theory    of    mammary 

gland,  45 

damage  to  the  optical  nerve,  30 

definition,  23 

dental  foci  of  infection,  34 

diet,  variations  in,  51 

due  to  placental  inf arcts  caused  by 

thrombosis  of  uterine  vessel,  34 

—  —  due    to    toxin    similar    to    that    of 

milk  fever  in  cattle,  45 

edema  of  the  legs,  with  high  blood- 
pressure,  31 

effect  of  a  chronic  septic  process 

on  the  kidneys,  35 

epilepsy,  differentiation  from,  52 

errors  of  metabolism,  50 

—  exophthalmic  goiter  in,  41,  42 
experimental  confirmation  of  mam- 
mary gland  theory,  45 

food,  in  relation  to,  51 


INDEX 


225 


Eclampsia,  etiology  and  symptomatol- 
ogy, frequency  of  occurrence,  23 

hydatidiform  mole  may  be  associ- 
ated with,  24 

hypertension  accepted  as  a  certain 

sign  of  toxemia,  30 

hysterical  and  cerebral  convulsions 

differentiated  from,  54 

in  puerperium,  29 

incidence  of,  in  different  seasons, 

chart  showing,  25 

infectious  other  than  renal,  34 

—  influence  of  seasons  on,  25 

. intermediary  products  in,  46 

—  internal  gland  function,  41 

—  intra-partum   type   is  assumed  the 

most  common,  27 

kidneys  and  their  role  in,  33 

lesion  of  kidney  as  primary  dis- 
turbance, 33 

leucin    as    a   product   of   autolysis, 

48 

—  lowered  protein  and  fat  in  diet  as 

a  detriment  to,  51 

—  mammary  gland  theory,  44 

—  merely  a  manifestation  of  anaphy- 

lactic  shock,  47 

—  more  prevalent  in  city  than  coun- 

try, 25 

—  mortality  higher  in  country,  25 

—  —  not  an  anaphylactic  phenomenon, 
48 

—  one  of  the  most  serious  complica- 

tions of  pregnancy,  23 

—  opotherapy,  41 

—  parental    introduction    of    complex 

protein,  48  •> 
peripheral  nerve  lesions,  29 

—  phosphorus  and  calcium,  need  for, 

in  blood  of  the  mother,  47 
placenta,  early  autolysis  of,  35 

—  premonitory  symptoms,  28 

presence    in    the   blood   of   certain 

taxis  substances,  50 

—  prognosis  for  the  fetus,  49 

recovery  may  follow  one  or  more 

convulsions,  23 
relation  between  anaphylaxis   and, 

49 

relief  of  the  pressure  on  the  kid- 
ney, 33 

—  renal  infection,  frequency  of,  33 
sensitization,   dissenting  views   on, 

48 
significance  of  high  blood-pressure, 

31 

symptoms,  27 


Eclampsia,  kidneys  and  their  role  in, 
toxemia  as  a  secondary  phenome- 
non, 33 

thyroid    and    parathyroid    opother- 
apy in  its  relation  to,  44 
—  thyroidectomy,  42,  43 

time  when  seizures  occur,  27 

• uremia,    differentiation    from,   52 

—  urine  in,  32,  33 

—  war  diet,  influence  of  the,  50 
where    deficient    thyroid    function 

thyroid  may  be  administered,  44 

—  where    seizure    comes    on    imme- 

diately before  labor,  28 
who  are  affected  by,  24 

—  without  convulsions,  29 

—  fatal  case  of,  hepatic  type,  214 

—  nephritic  type,  217 

—  fulminating,  with   recovery  and  sub- 

sequent death  from  cerebral  hemor- 
rhage, 209 

—  induction  of  labor,  version  and  death 

of  patient,  218 

—  numerous  convulsions,  with  recovery 

after  sedative  treatment,  219 

—  pathology,  63 

—  blood  must  circulate  round  poison- 

generating  foci  to  cause  toxemia, 

85 

cases  show  considerable  hemolysis, 

76 

cause  of  placental  poison,  theory 

of,  83 

cerebral  edema  as  a  cause  of,  80 

differential  diagnosis  of  condition^ 

resembling,  86 

experimental  reproduction  of,  car- 
ried out  in  guinea  pigs,  86 

hemorrhages,  78-80 

—  —  hemorrhages    more    numerous    in 

liver,  78 

hemorrhage  of  heart  and  other 

organs,  81 

hemorrhagic  lesions  noted  in  au- 
topsies of,  79 

hepatic  lesions,  72 

—  histology,  74 

liver  lesions  divided  into  four 

classes,  75 

no  relation  between  extent  of  neu- 
rotic process  and  severity  of  con- 
vulsions, 74 

origin  of  placental  infarction,  83- 

86 

—  oscular  lesions,  82 

—  predisposes    uterine    hemorrhages, 

81 


226 


INDEX 


Eclampsia,  pathology,  pulmonary  throm- 
bosis observed  in  hemorrhages,  78 

—  renal  lesions,  70 

summary   of    autopsy   findings   on, 

86 

traumatic  lesions,  81,  82 

—  treatment,  after  care,  122 

amount  of  glucose  injected,   141 

anomalies  in  placental  function  re- 
garded   as    indications    of    hys- 
terectomy, 134 
as  advanced  by  physicians,  123 

—  Stroganoff,  123,  124,  125 
Veit,  123 

Winckel,  123 

—  Zweifel,  124 

—  avoiding  irritability  of  the  eyes,  116 
bleeding,  as  a  former  means  of,  no 

—  blood-pressure,   115 

—  watched  carefully,  109 

—  blood  transfusion,  133 

—  carbohydrates  in,  135 

—  care  after  labor,  121 

—  care  of  the  organs  of  elimination, 

114 

—  Cesarean  section,  when  justifiable, 

128 

—  comparative  mortality  rates,   125 

—  complications,  122 

conservative   Stroganoff  treatment, 

no 

—  constipation,  correction  of,  113, 
convulsions,   116,   117 

decapsulation  of  kidney,  130,  131 

—  case  reports  of,  131 

—  delivery,  119 

description  of  the  treatment  of  an 

ordinary  case  of  convulsions,  117 
difficult   to    form   absolute   opinion 

as  to  value  of  vaginal  or  cesarean 

section,    128 
disturbances    of    kidney    function, 

138 
ductless  glandular  opotherapy  and 

serotherapy,    133 
elimination  of  care  and  worry,  112 

—  examination  of  urine,   1 14 

favorable  effects  of  excessive  car- 
bohydrate feeding,  136 

flushing  through  stomach,   134 

forcible  dilation  of  the  cervix  uteri 

formerly  practiced,  no 

general,  109 

glycemia  curve,  as  index  to  liver 

impairment,  141 

explanation  of  tables  of  cases, 

146-148 


Eclampsia,  treatment,  tables  of  cases  of 
estimations  of,  144,  145 

—  hemiplegia,  122 

—  individual  case  must  be  studied,  in 

—  induction  of  labor,  118 

injection    of    bicarbonate    of    soda 

as  stimulant  to  urination,  123 

—  in  last  two  centuries  vacillated  be- 

tween two  extreme  views,  no 
intestinal  tract  and  eyes  source  of 

trouble,  112 
intravenous    injection    of    glucose, 

138 
irrigation,  119 

—  labor,  desirability  of,  120 
laxatives,  1 13 

lumbar  puncture,  131 

magnesium  sulphate  in,  132 

normal  pregnancy  serum,  132 

other  plans  of,  123 

patient  should  be  seen  by  physician 

at    regular    intervals    in   preven- 
tive, 112 
preventive  measures,  in 

—  prophylactic  measures,  in 

rectal  examinations,  118 

rectal  infusions,  119 

• magnesium  sulphate,  133 

• rest    in    bed    an    important    factor 

in,  116 

—  retention  of  normal  metabolism,  114 

—  shock  must  be  avoided  in  labor  and 

delivery,  121 

skull  trephining,  131 

still  groping  for  a  method  that  will 

meet  specific  indications,  ill 
stomach  washing,  118 

—  sweat  packs,  120 

technic  of  preparation  and  injec- 
tion of  glucose,  139 

traumatized  tongue  great  source  of 

annoyance,  123 

urine  examinations  after  labor,  121 

use  of  enemas,  113,  118 

use  of  nitroglycerin  in  stout  pa- 
tients with  high  blood-pressure, 

US 
use  of  parathyroid  extracts  urged 

in,  .134 

—  vaginal  examinations,  118 

—  venesection,  129 

amount   of  blood  to  be   drawn, 

129 

leeches  formerly  used,  129 

—  one  of  the  oldest  procedures  in, 

129 
visual  disturbances,  116 


INDEX 


227 


Eclampsia,  uncertainty  regarding  etiol- 
ogy makes  modern  treatment  un- 
certain in,  ii 

—  vaginal  cesarean  section,  case  of,  216 
Eheler,    eclampsia    in    ruptured    extra- 
uterine  pregnancy,  24 

Encephalitis  lethargica,  confused  with 
eclampsia,  207 

Epilepsy,  differentiation  of  eclampsia 
and,  52 

Epileptic  seizures,  convulsions  mistaken 
by  earlier  writers  for,  2 

Etiology,  and  symptomatology,  acute  yel- 
low atrophy  of  the  liver,  20 

Fetal  origin,  evidence  of,  in  hyperemesis, 

65 

Fetus,  induction  of  labor  in  case  of 
toxemia,  for  death  of,  200 

—  prognosis  for,  49 

Gestation,  abnormal  forms  of,  associated 
with  eclampsia,  24 

—  in  epileptic  women,  2 
Glucose,  amount  injected,  140 

—  intravenous  injection  of,  138 

—  technic  of  preparation  and  injection 

of,  139 

—  use  of,  in  emaciation,  98 
Glycemia  curve,   as   index  to   liver  im- 
pairment, 140 

—  estimates,  142-148 

• — explanation  of  tables,  146-148 

—  table  of  cases  showing  estimations  of, 

144,  145 

Glycogen  deficiency,  19 
Goiter,  exophthalmic,   in  pregnancy,  41, 

42 
Graves  disease,  effect  on  toxemia,  41 

Hemorrhages,  concealed  internal,  due  to 
toxemias,  82 

—  eclampsia,  78 

—  hyperemesis,  66 

—  of  heart  and  other  organs,  81 

—  retinal,  82 

Hemorrhagic  lesions  in  brain,  79 
Hepatic    lesions,    acute   yellow    atrophy, 
pathology  of,  66 

—  eclampsia,  pathology  of,  72 

—  etiology  and  symptomatology  of,  18 

—  hyperemesis,  pathology  of,  64 
Herpes,  56 

Hospital  care,  104 

Hydatidiform  mole,  associated  with 
eclampsia,  24 


Hydramnios,  induction  of  labor  for, 
with  mild  toxemia  and  thyroid  dis- 
turbances, 205 

Hygiene,  general,  in  hyperemesis,  93 
Hyperemesis  gravidarum,  charts,  chem- 
ical   changes    in    blood    during, 
184 

—  high  ammonia  coefficient,  17 

—  urinary  conditions  in  case  of  neu- 

rotic vomiting,  16 

—  urinary,    from   a    case   of   toxemic 

vomiting,   18 

—  chemical    changes   in   blood,   acidosis, 

185 

—  analogous  to  those  in  post-partum 

eclampsia,  193 

—  carbon    dioxide    combining   power, 

decrease  of,   183 

—  during,   183-186 

—  table  showing,  184 

—  earliest  reference  to,  5 

—  etiology  and   symptomatology,   15 

—  acidosis,   high   ammonia   coefficient 

a  manifestation  of,  17 

—  chorea  formerly  regarded  in  same 

category  as,  53 

—  due  sometimes  to  a  toxemia  asso- 

ciated with  high  ammonia  coeffi- 
cient, 19 

—  glycogen  deficiency,  19 

—  hepatic  lesions,  18 

—  different  from  those  in  eclamp- 

sia, 1 8 
due    to     chloroform    poisoning, 

19 

—  due  to  ether  or  nitrous  oxide,  19 

—  high  ammonia  coefficient,  15 

—  chart  showing,  17 

—  how  to  distinguish  between  a  true 

toxemia  or  a  reflex  disturbance, 

I? 

—  nausea     and     vomiting     following 

manipulations    on    non-pregnant 
uterus,  15 

—  prognosis  of,  57 

—  toxic  and  psychic  factors,  15 

—  pathology,  63 

—  fetal  origin,  evidence  of,  65 

—  hemorrhages,  66 

—  hepatic  lesions,  64 

section    of    liver    from    a    fatal 

case  of,  64 
interpretation  of  findings,  66 

—  severe    case    of,    in    first    pregnancy, 

with    absence    in    subsequent   preg- 
nancies, 199 

—  treatment, 


228 


INDEX 


Hyperemesis  gravidarum,  treatment, 
abortion,  induction  of,  method, 
100-102 

—  acidosis    must    he    combated    in 

toxic  patient  before,   103 

—  lowered  blood-pressure  must  be 

combated,   103 

—  shock,   103 

—  should    not    be    delayed    beyond 

certain  limits,  100 

vaginal    hysterotomy    in    primi- 

parae,  102 

—  when  advisable,  99 

—  administration     of     sedatives     and 

narcotics,  97 

—  blood  transfusion,  108 
care,  routine  of,  97 

cauterization   of   cervical   erosions, 

93 

—  certain  amount  of  rest  in  addition 

to  usual  sleeping  period,  94 

—  corpus  luteum  extract,  95 

—  diet  schedule,  95 

—  general  hygiene,  93 

—  giving  of  water  and  food  by  rec- 

tum, 97 

—  hospital  care,  104 

in     nasopharyngeal     complications, 

107 

—  laxatives,  95 

meals  oftener  than  usual,  but  not 

so  much  food  at  a  time,  94 

—  nervous  system  must  be  put  at  rest, 

96 
no    attempt   to    introduce    nutrient 

materials  in  the  enemas,  99 
no   food  until   vomiting  begins  to 

lessen,  98 

—  physical  examination,  91 

production  of  saliva  seems  to  have 

favorable  effect,  94 

—  prognosis  after,  96 

—  retroflexion,  correction  of,  91 

—  salt   solution   under   no   considera- 

tion must  be  used,  98 

sedative  drugs, 

— cocain,  108 

—  ipecac,  108 

—  menthol,  108 

—  opium,  107 

• peppermint,  108 

sera    and    gland    extraction,    fetal 

serum,  105 

—  negative  results,  105 

—  placental  extracts,  105 

—  specific  drugs  to  overcome  nausta,  95 
stenosis  of  cervical  canal,  92 


Hyperemesis  gravidarum,  treatment, 
supplementary  measures,  104 

—  adrenalin  chlorid,  107 

—  sera  and  gland  extraction,   104- 

107 

—  thirst,  relief  of,  99 

use  of  alkali  and  sodium  bicarbon- 
ate, 98 

—  use  of  glucose  in  cases  of  emacia- 

tion, 98 

—  use   of  ordinary   retroversion  pes- 

sary, 92 
vomiting  will  cease  not  later  than 

fourth  month,  96 
where  retroverted  uterus  is  found, 

91 

—  uncertainty     as     to     etiology     makes 

modern  practice  uncertain  in,  n 
Hyperglycemia  in  eclampsia,   192 
Hysterical  convulsions,  54 
Hysterotomy,  vaginal,  in  primiparae,  102 

Icterus,   persistent,   in   pregnancy,   must 
be  regarded  with  apprehension,  20 
Indican,  urinary  analysis  of,  in  toxemias, 

157 

Infection,  as  factor  in  producing  eclamp- 
sia, 34 

—  dental  foci  of,  34 

Insanity,  arising  during  the  puerperium, 
is  possibility  of  a  toxemia,  30 

Intermediary  products,  in  eclamptic  in- 
toxication, 46 

Jaundice,  in  pregnancy  as  an  accidental 
symptom,  20 

Kidneys,  contain  the  greatest  amount  of 
creatinin,  173 

—  decapsulation  of,  130,  131 

—  case  reports  of,  131 

—  function  of,  cause  of  increase  in  urea 

nitrogen,  190 

—  in   eclampsia,   size  of,   is   not   dimin- 

ished, 71 

—  lesions  in,  18 

-  "of  pregnancy,"  21 

—  presence  of  a  chronic  septic  process 

on  the,  35 

—  role  of,  in  eclampsia,  33 

—  uric  acid  as  an  index  of  disturbance 

of  function,  190 

Labor,  care  of  patient  after,  121 

—  cases   on   induction    of,    for  toxemia, 

200-220 

—  desirability  of,  in  eclampsia,  120 

—  induction  of,  118 


INDEX 


229 


La  Vake,  theory  that  toxemia  is  due  to 
placental  infarcts,  34 

Laxatives,  95 

Lesions.     See  Hepatic,  Renal,  etc. 

Leucin,  48 

Lichtenstein,  mortality  rate  in  eclamp- 
sia, 

Liepman,  on  the  relation  of  anaphylaxis 
and  eclampsia,  49 

Literature  on  toxemias.  See  References 
to  Literature  on  Toxemias 

Liver,  acute  yellow  atrophy,  20 

—  glycemia-curve    as    index    to    impair- 

ment of,  140 

—  lesions  in,   19 

—  lesions  of,  divided  into  four  classes, 

75 

—  Schwangerschaftsleber  or  pregnancy, 

69 
Lumbar  puncture,  131 

—  magnesium  sulphate  in,  132 

—  normal  pregnancy  serum,  132 
Lynch,     cases     on     blood     pressure     in 

eclampsia,  30 

MacPherson,  mortality  rate  in  eclamp- 
sia, 125 

Magnesium  sulphate,  use  of,  in  lumbar 
puncture,  132 

Malaise,  symptom  of  eclampsia,  27 

Mammary  gland  theory,  44 

—  criticism  of  theory,  45 

—  experimental  confirmation  of,  45 

—  work  on  the  subject  done  with  cat- 

tle, 45 

Mauriceau,  practice  of,  in  the  eighteenth 
century,  2 

Metabolism,  errors  of,  50 

Mortality,  comparative  rates  in  treat- 
ment of  eclampsia,  125-128 

—  in  eclampsia,  statistics,  26 
Municipal  Health  Department,  statistics 

of  mortality  in  eclampsia,  26 

Nasopharyngeal  complications,  107 
Nephritic    toxemia,    blood    changes    in, 

179,  181 
—  table  showing  chemical,  180 

—  case  of  induction  of  labor  for  chronic, 

with  visual  complications,  216 

—  charts, 

table  showing  chemical  changes  in 

the  blood  in,  180 
• table  showing  retention  of  uric  acid, 

urea  and  creatinin  in  blood,  172 

—  direct  toxic   factor   is  cause  of   dis- 


turbance, not  mechanical  condition, 
22 

—  etiology   and   symptomatology   exten- 

sion of  process  into  preeclamptic 
toxemia  or  actual   eclampsia,  22 

—  frequently  a  forerunner  of  eclamp- 

sia, 51 
-  "kidney  of  pregnancy,"  21 

—  late  epidemic  of  influenza  cause  of 

increased,  21 

—  onset  is  gradual  in  most  cases,  21 
overburdening  the  maternal  kidney 

function  serves  as  starting  point 
for,  21 
prognosis  of,  57 

—  symptoms,  21 

—  pathology,  69,  70 

—  functional  renal  tests,  70 

—  treatment,  induction  of  labor,  203 
need    not    be    discussed    separately 

but  with  eclampsia,  109 
Newell,   F.   C.,  cases  on  blood-pressure 

in  eclampsia,  31 
New  York  Lying-in  Hospital,  influence 

of  seasons  on  eclampsia,  statistics, 

25 

—  mortality  of  eclampsia,  statistics,  26 

—  time  at  which  eclamptic  seizures  oc- 

cur, statistics,  27 
Nitrogen-partition,   urinary  analysis   of, 

in  toxemias,  158 
Nonprotein  nitrogen,  distribution  of,  in 

eclampsia,  193 

—  in  blood,  distribution  of,  169 

—  retention  of,  167,  169 
Nonprotein  nitrogen,  in  eclampsia,  186 

Opotherapy,  ductless  glandular,  in  ec- 
lampsia, 133 

—  relation  to  toxemias,  41 

—  thyroid  and  parathyroid,  44 
Oscular  lesions,  82 

Parathyroid  and  thyroid  opotherapy,  44 

Parturient  pareses,  clinical  and  patho- 
logical examination  of,  46 

Peripheral  nerve  lesions,  29 

Peterson,  Ruben,  mortality  rate  in  ec- 
lampsia, 126,  127 

Placenta,  case  of  severe  albuminuria,  39 

—  early  autolysis  of,  35,  36 

—  extract,   active  only  during  stage  of 

trophoblastic  development,   106 

—  advocated  in  case  of  hyperemesis, 

106 
statistics  in  cases  of,  use  of,  106 


230 


INDEX 


Placenta  infarcts,  maternal  origin  of,  85 

—  origin,  83 

—  pathology,  83 

—  two    theories    regarding   origin   of, 

«3 

—  premature  separation  of,  21 1 

—  section     of,     from     case     of     acute 

toxemia,  40 

—  from  case  of  albuminuria,  37 
showing  two  stages  in  the  infarc- 
tion process,  38 

Pre-eclamptic  toxemia,  case  of  induc- 
tion of  labor,  cervical  incision  and 
forceps,  206 

—  case  of,  with  Cesarean  section;  208 

—  charts,  blood-pressure,  showing  little 

effect  from  veratrum  viride,  120 

—  showing   blood-pressure   in  a   case 

of,  101 

—  chemical  changes  in  blood  in,  186 

—  table  showing,   188,  189 

—  etiology  and  symptomatology,   distin- 

guished from  nephritic  toxemia, 
22 

—  mental    disturbances,    and    loss    of 

sight,  22 

—  occurs  usually  between  seventh  and 

ninth  month,  22 

—  prognosis  of,  57 

—  reduction  of  amount  of  urine,  23 

—  pathology,  69,  70 

—  functional  renal  tests,  70 

—  treatment,  need  not  be  separately  dis- 

cussed, but  with  eclampsia,  109 
Pregnancy,    blood    changes    in    normal, 
178,  179 

—  exophthalmic     goiter     occurring     in, 

rare,  41,  42 

—  mortality  of  chorea  in,  53 
• —  symptoms  of  chorea  in,  53 

—  table    showing   composition   of   blood 

in  normal,  179 

—  thyroidectomy,  effect  of,  on,  42 
Presumable      toxemias,       angioneurotic 

edema,  57 

—  skin  eruptions,  55 

—  herpes,  56 

—  pruritus,  56 

—  purpuria,  56 

—  urticaria,  57 

Prognosis  in  toxemias  of  pregnancy,  57 
Prophylaxis,     demands     that     pregnant 
woman's  diet  contain  enough  min- 
eral substances,  47 

—  may   be   the    source   of   clearing   up 

problems  of  toxemias,  12 
• — measures  of,  in  eclampsia,  in 


Pruritus,  56 

Puerperium,   eclampsia  developing  dur- 
ing, 29 
Purpuria,  56 

—  etiology  and  .symptomatology,  attacks 

primiparae   more    often    than   mul- 
tiparae,  21 

Rectal  examinations,  in  eclampsia,   118 
Rectal  infusions,  119 

—  magnesium  sulphate,  133 
Recurrence  of  toxemias,  case  in  which 

patient  was  subject  to  seizures  dur- 
ing four  successive  years,  59 

—  hospital  statistics  as  to,  58 
References  to  literature  on  toxemias,  197 

—  chemical   changes    in   the   blood,    197, 

198 

—  on  etiology  and  symptomatology,  59- 

62 

—  pathology,  87-89 

—  treatment,  149-152 

—  urinary  conditions,  164,  165 

Renal  infection,  case  of  induction  of 
labor  for  death  of  fetus  and 
toxemia,  200-202 

—  frequency  of,  33 

Renal  lesions,  acute  yellow  atrophy 
pathology  of,  66 

—  eclampsia,  pathology  of,  70 

—  hyperemesis,  pathological  aspects  of, 

65 
Rest-nitrogen,  in  blood,  169 

—  in  eclampsia,  187 
Retroflexion,  correction  of,  91 

Salivation,  increased,  55 

Schwangerschaftsleber  or  pregnancy 
liver,  69 

Seasons,  influence  of,  on  eclampsia,  25 

Sensitization,  dissenting  views  on,  48 

Serotherapy,  ductless  glandular,  in  ec- 
lampsia, 133 

Skull  trephining,  131 

Starvation,  effect  on  ammonia  coeffi- 
cient, 155 

Statistics,  frequency  of  eclampsia,  23 

—  influence  of  seasons  on  incidence  of 

eclampsia,  25 

—  mortality  of  eclampsia,  26 
Stomach  flushing,  118 

—  in  eclampsia,  134 

Stroganoff,  mortality  rates  in  eclampsia, 
125 

—  theory    of    infections     as     cause    of 

eclampsia,  34 

—  treatment  in  eclampsia,  123-125 


INDEX 


231 


Thirst,  relief  of,  99 

Thyroid  disturbances,  case  of  induction 
of  labor  for  toxemia  and,  204 

Thyroid  opotherapy,  44 

Thyroidectomy,  discussion  of  a  case  of, 
at  New  York  Academy  of  Medi- 
cine, 43 

—  effect  of,  on  pregnancy,  42 

—  recent  clinical  study  by  H.  F.  Watson, 

43 

Titus,  Dr.,  on  method  of  excessive  car- 
bohydrate feeding  in  toxemias,  136- 
138 

Toxemia,  208 

—  cardiac  disease  associated  with,  208 

—  induction  of  labor,  for  a  mild,  202 

—  and  hydramnios,  205 

and   thyroid   disturbances,   204 

for  death  of  fetus  and,  200 

for  progressive,  210 

in  middle  months  of  pregnancy,  215 

—  marked,  in   middle  months   of  preg- 

nancy, 212 

—  premature     separation     of     placenta 

with,  211 

—  spontaneous  abortion  during,  213 
Toxemias,    of    pregnancy,    blood    must 

circulate    around   poison-generating 
foci  to  cause,  85 

—  cases  demonstrating  typical  instances 

of,  199-220 

—  chorea,  a  complication  to  be  carefully 

watched,  54 

—  classification  of,  14 

—  clinical    knowledge    of,    has    been    in 

existence  for  several  centuries,  II 

—  conceptions  of,  held  in  early  part  of 

nineteenth  century,  clouded,  6 

—  deaths  from,  exceeded  only  by  those 

from  "puerperal  septicemia,"  27 

—  development      of      blood      chemistry 

opened  a  new  field  of  research,  63 

—  development    of,     from     the     earlier 

"humours,"  I 

—  due  to  autolytic  products  liberated  in 

early  stages  of  placental  death,  36, 

85 

—  earliest  references  to,   I 

—  employment  of  carbohydrates  in  treat- 

ment of,  135 

—  exophthalmic  goiter  in,  rare,  41,  42 

—  failure  of  the  thyroid  gland  as  a  cause 

of,  41 

—  historical,  1-12 

—  hypertension    accepted    as    a    certain 

sign  of,  30 

—  increased  salivation,  55 


Toxemias,   mortality   and   incidence   of, 
still  remains  high,   II 

—  pathological  aspects  of,  63 

—  practice  of  earlier  doctors,  2 

—  Amberg,  2 
-  Bard,  5 

—  Baudelocque,  5 

—  Blundell,  James,  9-11 

—  Burton,  3 

—  Burus,  John,  6-9 

—  Coudray,  Madame  Le  Boursier  du, 

chief  midwife  of  Paris,  3 
—  Hamilton,  4 

—  Jackson,  S.  H.,  5 

—  Mauriceau,  2 

—  predispose  to  uterine  hemorrhages,  81 

—  prophylaxis    may    prove    solution    of 

problem  in,  12 

—  prognosis  for  the  fetus,  49 

—  prognosis  in,  57 

—  recurrence  of,  58 

—  relation  of  chorea  to,  54 

—  summary  as  to  treatment  of,  148,  149 

—  theory  of  disturbances  in  metabolism 

causing  all,  14 

—  blood,  urine  and  histologic  studies 

indicate  essential  differences,  14 

—  Williams,    J.     Whitridge    combats 

this  theory,  14 
• —  treatment  of,  90 

—  uncertainty     as     to     etiology     makes 

modern  practice  uncertain  in,  II 

—  urinary    conditions    associated    with, 

I53-I65 

Traumatic  lesions,  81,  82 
Treatment  of  toxemias.     See  Toxemia 

—  divided    into    two    divisions    in    this 

work,  91 

—  general  remarks,  90 

Umbilical  vein  and  artery,  blood  changes, 
in  eclampsia,  194,  195 

—  table  showing  chemical  changes,   194 
Urea,  in  eclampsia,  187 

Urea  nitrogen,  in  blood,  169 

Uremia,    differentiation    of     eclampsia, 

and,  52 
Uric  acid,  in  blood,  170 

—  increase  of,  171 

—  retention  of,  171 

—  in  eclampsia,  187 

Urinary  conditions  in  toxemias,  acidosis, 

155,  159 

—  altered  chemical  composition  studied, 

154 

—  amino-acids,  155 

—  ammonia  coefficient,  154 


232 


INDEX 


Urinary  conditions   in  toxemias,  analy- 
sis of,  156 

—  albumin  and  casts,  157 

—  bile  pigment,  159 

—  chlorids,  156 

—  indican,  157 

—  nitrogen  partition,   158 

—  urea,  156 

—  urobilin,  159 

—  volume,  156 

—  bile  pigment,  155 

—  desirability   of   periodic   examination, 

153 

—  differential  diagnosis,  160-164 

—  in  eclampsia,  161 

—  in  hyperemesis,  160 

—  in  nephritis,  162 

—  acute,  162 

—  chronic  interstitial,  163 

—  chronic  parenchymatous,   163 

—  in  neurosis,  161 

—  in  stasis  and  renal  hyperema,  162 

—  toxemia  of  pregnancy,  160-164 

—  popular  belief,  the  urine  of  pregnancy 

toxic  to  animals,  153 

—  relatively  little  of  clinical  value  deter- 

mined as  to  toxicity,  153 

—  search    for    toxin    in    urine    remains 

fruitless,  154 

—  starvation,  155 

Urine,  in  eclamptic  seizure,  32 

—  specific     gravity     high     and     acidity 

marked,  32 

—  sugar  rarely  found  in  eclamptic,  46 


Urobilin,    urinary   analysis   of,   in   tox- 
emias, 159 
Urticaria,  56,  57 

Vaginal  examinations,  in  eclampsia,  118 
Veit,  treatment  of  eclampsia,  123 
Venesection,  129 

—  amount  of  blood  to  be  drawn,  129 

—  one  of   oldest  methods  of  procedure 

in  eclampsia,  129 
Visual  disturbances,  116 
Vomiting  of  pregnancy.    See^  Hypereme- 
sis Gravidarum 

War  diet,  influence  of,  on  eclampsia,  50, 

51 

Ward,  George  Gray,  Jr.,  use  of  a  saline 
extract  of  thyroid  proteins  of  hu- 
man glands,  41 

Watson,  E.  P.,  case  of  eclampsia  re- 
covery, 24 

Williams,  J.  Whitridge,  first  to  show 
high  ammonia  coefficient  in  urine 
in  true  toxemia,  17 

—  points    out   that    women    giving    pre- 

mature birth  are  liable  to  nephritic 
toxemia,  22 

—  theory    of    disturbed    metabolism    as 

cause  of  toxemias  combated  by,  14 
Winckel,  treatment  in  eclampsia,  123 

Young,  on  theory  of  origin  of  placental 
infarcts,  84 

Zweifel,  treatment  of  eclampsia,  125 


(1) 


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